Academic Secretary to the University, Stanford University (2007 - 2014)
Honors & Awards
Rhodes Scholar, Rhodes Trust (1955 - 1957)
Guggenheim Fellow, John Simon Guggenheim Foundation (1977 - 1978)
Fellow, American College of Physicians (1985)
Fellow, Royal College of Physicians (London) (1998)
Champion of Hope Award, National Kidney Foundation of Northern California (1999)
Commendation, Department of Veterans Affairs (2003)
Lifetime Honorary Medical Staff Appointment, Stanford Hospital and Clinics (2014)
Boards, Advisory Committees, Professional Organizations
Member, Sequoia Living Board of Directors (2018 - Present)
President, Sequoias of Portola Valley Resident Association Board of Directors (2015 - 2016)
A.B., University of Iowa, General Science (1955)
B.A., Oxford University, Physiology (1957)
M.D., Harvard Medical School, Medicine (1960)
M.A., Oxford University, Physiology (1961)
Community and International Work
Rhodes Marshall Panel, Stanford University, Stanford University
Rhodes and Marshall Scholarships
American Rhodes Scholars; American Marshall Scholars
Opportunities for Student Involvement
Homocysteine Study (HOST)
The primary objective of this study is to test the hypothesis that administration of folate, pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) in high doses to patients with advanced chronic renal failure or end stage renal disease and abnormally high plasma homocysteine levels will lower the homocysteine levels and the death rate compared to patients who receive placebo. The secondary objective is to test the hypothesis that intake of the vitamins compared to placebo decreases the incidence of myocardial infarction, disabling stroke, and amputation of a lower extremity and, in hemodialysis patients, thrombosis of the vascular access.
Stanford is currently not accepting patients for this trial.
- Space exploration. American journal of physiology. Renal physiology 2015; 309 (12): F1003-4
Resolving an 80-yr-old controversy: the beginning of the modern era of renal physiology
ADVANCES IN PHYSIOLOGY EDUCATION
2014; 38 (4): 286-295
Marcello Malpighi discovered the glomerulus that bears his name in the 17th century, but it was not until the middle of the 19th century, in 1842, that William Bowman in London published his studies of the histological structure of the glomerulus and proposed that urine formation begins with glomerular secretion. At nearly the same time in Marburg, Carl Ludwig, unaware of Bowman's findings, proposed that urine formation begins with glomerular filtration followed by tubule reabsorption. The controversy lasted 80 yr. Prominent investigators weighed in on both sides. Rudolph Heidenhain's findings in 1874 swung the pendulum toward Bowman's theory until Arthur Cushny published his book, The Secretion of Urine, in 1917, in which he found the evidence insufficient to prove either theory. In 1921, a young physician, Joseph Wearn, began his postresidency training in the laboratory of Alfred N. Richards. He read Cushny's book and learned how to expose the glomerulus of a living frog. Richards proposed that Wearn use that experimental preparation to inject epinephrine into the glomerulus. Wearn proposed a different experiment: instead of using injection, collect fluid from the glomerulus and analyze it. Richards agreed, and the landmark results of that experiment, published in 1924, settled the controversy. The modern era of renal physiology was born.
View details for DOI 10.1152/advan.00105.2014
View details for Web of Science ID 000345898500002
View details for PubMedID 25434011
Medication adherence assessment in a clinical trial with centralized follow-up and direct-to-patient drug shipments.
2013; 10 (3): 441-448
Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel.To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up.Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (≥85.7%) and liberal (≥71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures.Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p = 0.005 for the stringent and p = 0.003 for the liberal definition; questionnaire: p = 0.002 for both adherence definitions).Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias.Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required.
View details for DOI 10.1177/1740774511410331
View details for PubMedID 21813583
Effects of Lowering Homocysteine Levels With B Vitamins on Cardiovascular Disease, Cancer, and Cause-Specific Mortality Meta-analysis of 8 Randomized Trials Involving 37 485 Individuals
ARCHIVES OF INTERNAL MEDICINE
2010; 170 (18): 1622-1631
Elevated plasma homocysteine levels have been associated with higher risks of cardiovascular disease, but the effects on disease rates of supplementation with folic acid to lower plasma homocysteine levels are uncertain. Individual participant data were obtained for a meta-analysis of 8 large, randomized, placebo-controlled trials of folic acid supplementation involving 37 485 individuals at increased risk of cardiovascular disease. The analyses involved intention-to-treat comparisons of first events during the scheduled treatment period. There were 9326 major vascular events (3990 major coronary events, 1528 strokes, and 5068 revascularizations), 3010 cancers, and 5125 deaths. Folic acid allocation yielded an average 25% reduction in homocysteine levels. During a median follow-up of 5 years, folic acid allocation had no significant effects on vascular outcomes, with rate ratios (95% confidence intervals) of 1.01 (0.97-1.05) for major vascular events, 1.03 (0.97-1.10) for major coronary events, and 0.96 (0.87-1.06) for stroke. Likewise, there were no significant effects on vascular outcomes in any of the subgroups studied or on overall vascular mortality. There was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years of it. Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.
View details for Web of Science ID 000282917600001
View details for PubMedID 20937919
Homocysteine Lowering and Cognition in CKD: The Veterans Affairs Homocysteine Study
AMERICAN JOURNAL OF KIDNEY DISEASES
2009; 54 (3): 440-449
Individuals with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) have high plasma total homocysteine (tHcy) levels, which may be a risk factor for cognitive impairment. Whether treatment with high-dose B vitamins to decrease high tHcy levels improves cognition in persons with kidney disease is unknown.Randomized controlled trial.A substudy of 659 patients (mean age, 67.3 +/- 11.7 years) who participated in a randomized double-blind clinical trial 5 years in duration conducted in 36 US Department of Veterans Affairs medical centers of the effect on all-cause mortality of vitamin-induced lowering of plasma tHcy level. 236 (35.8%) were treated by using dialysis (ESRD) and 423 (64.2%) had a Cockcroft-Gault estimated creatinine clearance of 30 mL/min or less (advanced CKD). All had high tHcy levels (> or =15 micromol/L) at baseline. Cognitive assessments began during the follow-up period of the main trial 3 years after treatment began; participants subsequently were retested 1 year later to assess cognitive change.Daily high-dose B vitamin capsule (40 mg of folic acid, 100 mg of vitamin B(6), and 2 mg of vitamin B(12)) or placebo.Cognitive function at initial assessment and 1 year later.Telephone Interview of Cognitive Status-modified, supplemented with attention, working memory, and executive function tests.Initial cognitive function was impaired in approximately 19% of patients regardless of treatment assignment (vitamin or placebo) or kidney disease status (advanced CKD or ESRD). Treatment decreased tHcy levels by 26.7%. Unadjusted and adjusted analyses showed that treatment did not improve initial cognitive outcomes or affect subsequent cognitive status 1 year later.Cognitive assessments began after treatment was initiated; cognitive assessment was limited.Treatment with high daily doses of B vitamins, which decreased tHcy levels, did not affect cognitive outcomes in patients with advanced CKD and ESRD.
View details for DOI 10.1053/j.ajkd.2009.05.013
View details for Web of Science ID 000269640600010
View details for PubMedID 19628319
View details for PubMedCentralID PMC2748786
Effect of the MTHFR C677T and A1298C Polymorphisms on Survival in Patients With Advanced CKD and ESRD: A Prospective Study
AMERICAN JOURNAL OF KIDNEY DISEASES
2009; 53 (5): 779-789
Abnormalities in the gene regulating methylenetetrahydrofolate reductase (MTHFR) are associated with increased homocysteine levels and increased mortality in normal and chronic kidney disease (CKD) populations.Gene association study.This was a substudy of 677 patients from 21 Veterans Affairs medical centers participating in a randomized clinical trial (Homocysteinemia in Kidney and End-Stage Renal Disease [HOST]) of the effect on all-cause mortality of vitamin-induced lowering of plasma homocysteine levels. Of 677 patients, 213 (31%) were treated by using dialysis (end-stage renal disease [ESRD]) and 464 (69%) had a Cockcroft-Gault estimated creatinine clearance less than 30 mL/min (advanced CKD).Polymorphisms C677T (rs1801133) and A1298C (rs1801131) of the MTHFR gene.Unadjusted and adjusted all-cause mortality.DNA was extracted from blood samples and amplified by means of polymerase chain reaction.The adjusted hazard ratio in a recessive model of the relationship between the C677T polymorphism and all-cause mortality in all patients was 1.47 (95% confidence interval, 1.00 to 2.16; P = 0.05). In patients with ESRD with the mutant TT genotype, the adjusted hazard ratio for mortality in all patients was 2.27 (95% confidence interval, 1.07 to 4.84; P = 0.03); patients with advanced CKD showed a similar, although not significant, trend. The risk of myocardial infarction (P = 0.05) and composite risk of myocardial infarction, stroke, lower-extremity amputation, and mortality (P = 0.02) were greater in patients with ESRD with the mutant T allele at nucleotide 677. The overall relationship between the A1298C polymorphism and mortality was not significant (P = 0.6).Participants were 98% men; DNA samples were not obtained at enrollment in HOST; linkage disequilibrium with another causal polymorphism is a potential confounding factor; and power was reduced by the limited number of participants.These findings provide additional support for the hypothesis that the mutant TT genotype at nucleotide 677 of the gene regulating MTHFR activity may increase the mortality risk in patients with ESRD.
View details for DOI 10.1053/j.ajkd.2008.12.023
View details for Web of Science ID 000265923500010
View details for PubMedID 19272686
Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease - A randomized controlled trial
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
2007; 298 (10): 1163-1170
High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L).Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo.The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients.Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups.Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.clinicaltrials.gov Identifier: NCT00032435.
View details for Web of Science ID 000249374200021
View details for PubMedID 17848650
Countercurrent exchange in the renal medulla
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
2003; 284 (5): R1153-R1175
The microcirculation of the renal medulla traps NaCl and urea deposited to the interstitium by the loops of Henle and collecting ducts. Theories have predicted that countercurrent exchanger efficiency is favored by high permeability to solute. In contrast to the conceptualization of vasa recta as simple "U-tube" diffusive exchangers, many findings have revealed surprising complexity. Tubular-vascular relationships in the outer and inner medulla differ markedly. The wall structure and transport properties of descending vasa recta (DVR) and ascending vasa recta (AVR) are very different. The recent discoveries of aquaporin-1 (AQP1) water channels and the facilitated urea carrier UTB in DVR endothelia show that transcellular as well as paracellular pathways are involved in equilibration of DVR plasma with the interstitium. Efflux of water across AQP1 excludes NaCl and urea, leading to the conclusion that both water abstraction and diffusion contribute to transmural equilibration. Recent theory predicts that loss of water from DVR to the interstitium favors optimization of urinary concentration by shunting water to AVR, secondarily lowering blood flow to the inner medulla. Finally, DVR are vasoactive, arteriolar microvessels that are anatomically positioned to regulate total and regional blood flow to the outer and inner medulla. In this review, we provide historical perspective, describe the current state of knowledge, and suggest areas that are in need of further exploration.
View details for DOI 10.1152/ajpregu.00657.2002
View details for Web of Science ID 000182018000002
View details for PubMedID 12676741
- Reflections by Rex L. Jamison The Stanford Senate of the Academic Council. Reflections on Fifty Years of faculty Governance, 1968-2018. edited by Stansky, P., Ris, E. W., Schofield, S. W., et al Stanford University Office of the Academic Secretary with the support of the Stanford Historical Society. 2018: 180–185
Homocysteine-lowering trials for prevention of cardiovascular events: A review of the design and power of the large randomized trials
AMERICAN HEART JOURNAL
2006; 151 (2): 282-287
Dietary supplementation with folic acid and vitamin B12 lowers blood homocysteine concentrations by about 25% to 30% in populations without routine folic acid fortification of food and by about 10% to 15% in populations with such fortification. In observational studies, 25% lower homocysteine has been associated with about 10% less coronary heart disease (CHD) and about 20% less stroke.We reviewed the design and statistical power of 12 randomized trials assessing the effects of lowering homocysteine with B-vitamin supplements on risk of cardiovascular disease.Seven of these trials are being conducted in populations without fortification (5 involving participants with prior CHD and 2 with prior stroke) and 5 in populations with fortification (2 with prior CHD, 2 with renal disease, and 1 with prior stroke). These trials may not involve sufficient number of vascular events or last long enough to have a good chance on their own to detect reliably plausible effects of homocysteine lowering on cardiovascular risk. But, taken together, these 12 trials involve about 52,000 participants: 32,000 with prior vascular disease in unfortified populations and 14,000 with vascular disease and 6000 with renal disease in fortified populations. Hence, a combined analysis of these trials should have adequate power to determine whether lowering homocysteine reduces the risk of cardiovascular events within just a few years.The strength of association of homocysteine with risk of cardiovascular disease may be weaker than had previously been believed. Extending the duration of treatment in these trials would allow any effects associated with prolonged differences in homocysteine concentrations to emerge. Establishing a prospective meta-analysis of the ongoing trials of homocysteine lowering should ensure that reliable information emerges about the effects of such interventions on cardiovascular disease outcomes.
View details for DOI 10.1016/j.ahj.2005.04.025
View details for Web of Science ID 000235521100005
View details for PubMedID 16442889
- Design and statistical issues in the Homocysteinemia in Kidney and End Stage Renal Disease (HOST) Study. Clinical Trials 2004; 1 (5): 451-460
Urinary concentrating mechanism
MEMBRANE TRANSPORT AND RENAL PHYSIOLOGY
2002; 129: 177-192
View details for Web of Science ID 000177649700010
Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
1995; 6 (6): 1552-1558
Natriuretic peptide receptor B (ANP-RGC(B)) has been previously identified in the kidney. It binds C-type natriuretic peptide (CNP) with high affinity and the two other natriuretic peptides (atrial natriuretic peptide and brain natriuretic peptide) with low affinity, and mediates the biological effects of CNP. The purpose of this investigation was to identify sites of ANP-RGC(B) mRNA in the rat renal tubule and to confirm that CNP itself is synthesized in the rat kidney. Kidneys from male Sprague-Dawley rats were removed and divided into cortex, outer medulla, and inner medulla. Using reverse transcriptase and polymerase chain reaction techniques, ANP-RGC(B) mRNA was identified in the three principal regions of the kidney. Individual glomeruli and segments of the renal tubule were microdissected and subjected to reverse transcriptase-polymerase chain reaction. ANP-RGC(B) mRNA was regularly found (>60% of animals) in glomeruli, distal convoluted tubule, and cortical, outer medullary, and inner medullary tubules but not in the proximal convoluted tubule, proximal straight tubule, thin or medullary thick ascending limb. ANP-RGC(B) mRNA was also identified in outer medullary descending vasa recta. Glyceraldehyde-3-phosphate-dehydrogenase and natriuretic peptide A receptor mRNA were present in all segments. In a separate study, CNP mRNA was identified in whole kidney, cortex, and medulla. These findings confirm that CNP and its receptor are present in the rat kidney. The proximity of the ligand and receptor suggests that CNP may have paracrine or autocrine regulatory functions in the rat kidney.
View details for Web of Science ID A1995TL77400005
View details for PubMedID 8749680
- RENAL EFFECTS OF SEVOFLURANE ANESTHESIOLOGY 1995; 83 (3): 443-445
DETERMINATION OF BLOOD-FLOW TO THE TRANSPLANTED KIDNEY - A NOVEL APPLICATION OF PHASE-CONTRAST, CINE MAGNETIC-RESONANCE-IMAGING
1994; 57 (10): 1445-1450
There is at present no noninvasive method that reliably measures blood flow in the poorly functioning renal allograft. The present study was designed to evaluate phase-contrast cine magnetic resonance imaging (PC-cine-MRI) for this purpose. We recruited for study 18 patients who had received kidney transplants 13-66 months earlier from closely related living donors. As judged by the glomerular filtration rate, which was elevated for a single kidney (76 +/- 4 ml/min 1.73 m2), allograft function was excellent, permitting the assumption of unimpaired renal extraction of paminohippuric acid (PAH). Allograft blood flow was determined consecutively on the same day, first by the standard PAH clearance technique and they by the product of the velocity of protons and renal vein cross-sectional area using PC-cine-MRI. MRI determinations could not be completed because of claustrophobia in two patients and failure to image the terminus of the allograft vein another two. Comparison of blood flow in the remaining 14 subjects revealed the two techniques to be strongly related (r = 0.91, P < 0.001). On the average, the renal blood flow rate was similar by each method; 732 +/- 62 by PAH clearance and 703 +/- 69 ml/min by PC-cine-MRI, but the agreement among individuals between the two methods was only modest, with a 95% confidence interval of agreement from -214 to +254 ml/min. We conclude that PC-cine-MRI provides a fairly accurate and noninvasive method for determining the rate of blood flow in the transplanted kidney. With further refinement it should permit the role of depressed blood flow in a variety of acute and chronic forms of human allograft dysfunction to be elucidated in humans for the first time.
View details for Web of Science ID A1994NP05700007
View details for PubMedID 8197605
TRANSPORT OF SODIUM AND UREA IN OUTER MEDULLARY DESCENDING VASA-RECTA
JOURNAL OF CLINICAL INVESTIGATION
1994; 93 (1): 212-222
We dissected and perfused outer medullary vasa recta (OMVR) from vascular bundles in the rat. Permeabilities of sodium (PNa) and urea (Pu) were simultaneously determined from the lumen-to-bath efflux of 22Na and [14C]urea. PNa and Pu were also measured by in vivo microperfusion of descending (DVR) and ascending vasa recta (AVR) at the papillary tip of Munich-Wistar rats. In some OMVR PNa was indistinguishable from zero. The mean +/- SE of PNa (x 10(-5), cm/s) in OMVR was 76 +/- 9. Pu in OMVR was always very high (x 10(-5), cm/s), 360 +/- 14. There was no correlation between OMVR PNa and Pu. Inner medullary AVR and DVR had PNa of 115 +/- 10 and 75 +/- 10, respectively, and Pu of 121 +/- 10 and 76 +/- 11, respectively. PNa and Pu in papillary vasa recta were always nearly identical and highly correlated. Transport of [14C] urea in OMVR was reversibly inhibited by addition of unlabeled urea or phloretin to the bath and lumen, providing evidence for carrier-mediated transport. These data suggest that sodium and urea might traverse the wall of inner medullary vasa recta by a paracellular pathway while urea also crosses by a transcellular route in OMVR. Electron microscopic examination of seven in vitro perfused OMVR revealed no fenestrations and exposure of these vessels to 10 microM calcium ionophore A23187 or 1 nM angiotensin II resulted in reversible contraction, suggesting that in vitro perfused OMVR are DVR only.
View details for Web of Science ID A1994MY15900029
View details for PubMedID 8282790
View details for PubMedCentralID PMC293755
REGULATION OF PLATELET CLEARANCE RECEPTORS FOR ATRIAL-NATRIURETIC-PEPTIDE IN DIABETIC NEPHROPATHY
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
1992; 3 (2): 236-243
The findings that circulating levels of atrial natriuretic peptide (ANP) are elevated in diabetic nephropathy and that the magnitude of the urinary excretion rate of cGMP in response to hypervolemia-induced ANP release is blunted have recently been reported. The purpose of this study was to determine whether these abnormalities are associated with the down-regulation of ANP receptors. Because biologically active (A) ANP receptors in the kidney are inaccessible, we have examined the binding of (125I alpha)ANP to clearance (C) receptors on platelets obtained from patients with diabetic nephropathy. Scatchard analysis revealed a reduction in such binding sites compared with those in healthy controls: 12 +/- 2 versus 19 +/- 2 per platelet, respectively (P less than 0.001). The dissociation constant, Kd, was higher: 66.7 +/- 33.1 versus 38.5 +/- 11 pM, respectively (P less than 0.02). The reduced number of receptors could reflect the down-regulation of ANP C receptors in response to an elevation of plasma levels of ANP, the median value of which was 10.6 versus 7.1 pmol/L in controls (P less than 0.05). Alternatively, the findings could represent a primary adaptation by C receptors to elevate plasma ANP levels and increase the availability of the peptide to biologically active renal receptors. The latter adaptation would serve to mitigate the sodium retention that attends diabetic nephropathy.
View details for Web of Science ID A1992JK69400013
View details for PubMedID 1327260
NORMAL RENAL BLOOD-FLOW MEASUREMENT USING PHASE-CONTRAST CINE MAGNETIC-RESONANCE-IMAGING
1992; 27 (6): 465-470
This study assesses the ability of a cardiac-gated phase-contrast magnetic resonance imaging (MRI) technique to measure renal blood flow (RBF) noninvasively in humans.In nine normal volunteers, total RBF in the renal arteries and in the left renal vein was estimated by MRI and correlated with RBF determined by the clearance of para-aminohippuric acid (CPAH) and the hematocrit level.Correlation of RBF estimated from left renal vein flow, with RBF by CPAH-hematocrit, yielded r = .86 (P less than .003). Repeated measurement of RBF by MRI demonstrated a high degree of reproducibility, with coefficients of variation ranging from 4.8% to 8.9%. However, the MRI measurements of arterial flow did not significantly correlate with the standard measurements.Reproducible noninvasive measurement of normal RBF is possible with the phase-contrast MRI technique used to measure renal venous blood flow.
View details for Web of Science ID A1992HX03500010
View details for PubMedID 1607260
- Urinary concentration and dilution: physiology. Handbook of Physiology. Sect.8: Renal Physiology. New York:Oxford University Press 1992: 1219-1279
RESISTANCE OF DESCENDING VASA RECTA TO THE TRANSPORT OF WATER
AMERICAN JOURNAL OF PHYSIOLOGY
1990; 259 (4): F688-F697
The effect of varying intracapillary oncotic pressure on the rate of transcapillary volume flux in microperfused descending vasa recta (DVR) was studied during furosemide diuresis in the Munich-Wistar rat. At the papillary base, plasma protein concentration and hydraulic pressure were 5.7 +/- 0.1 g/dl and 11.7 +/- 0.7 mmHg in nonperfused DVR, respectively, and 5.6 +/- 0.1 g/dl and 9.4 +/- 0.4 mmHg in nonperfused ascending vasa recta (AVR), respectively. These results demonstrate that the papillary microcirculation does not remove water from the interstitium during furosemide diuresis and defines Starling forces in the pericapillary interstitium. Osmolality and urea concentration were 380 +/- 11 mosmol/kgH2O and 56 +/- 5 mM in DVR plasma at the papillary base, respectively, and 386 +/- 10 mosmol/kgH2O and 62 +/- 5 mM in DVR plasma at the tip, respectively. These results demonstrate abolition of corticomedullary small solute gradients. DVR were perfused at a rate of 10 nl/min with a buffer solution containing small-solute concentrations that matched those of plasma in nonperfused DVR. The buffer solution also contained 2 x 10(6) mol wt fluorescein isothiocyanate-labeled dextran (FITC-Dx, 5 mg/ml) and either 0.1 or 5.0 g/dl albumin. Microperfused DVR were punctured a second time downstream of the perfusion site for sample collection or servo-nulling pressure measurement. The rate of transmembrane volume flux, determined from the change in FITC-Dx concentration from perfusate to collectate, was 0.99 +/- 0.29 nl.min-1.mm-1 when perfusate contained 0.1 g/dl albumin and 0.00 +/- 0.23 nl.min-1.mm-1 with 5.0 g/dl albumin (P less than 0.01). Intracapillary hydraulic pressures were 21.7 and 20.4 mmHg during microperfusion of DVR with 0.1 and 5.0 g/dl albumin, respectively. These results demonstrate that transcapillary driving forces of 20 mmHg (5 g/dl albumin) influence transcapillary water movement across the DVR endothelium. For an average capillary diameter of 12.9 microns, DVR hydraulic conductivity is calculated to be greater than 1.4 x 10(-6) cm.s-1.mmHg-1.
View details for Web of Science ID A1990EE02200092
View details for PubMedID 1699435
- RENAL MEDULLARY MICROCIRCULATION PHYSIOLOGICAL REVIEWS 1990; 70 (3): 885-920
EFFECT OF SMALL-SOLUTE GRADIENTS ON TRANS-CAPILLARY FLUID MOVEMENT IN RENAL INNER MEDULLA
AMERICAN JOURNAL OF PHYSIOLOGY
1989; 257 (4): F547-F553
Volume efflux from descending vasa recta (DVR) of hydropenic rats occurs despite a higher oncotic pressure than hydraulic pressure. To explain this, we previously proposed that transcapillary small-solute gradients exert an additional driving force for volume efflux. This hypothesis was tested by micropuncture of DVR at the base and tip of the exposed renal papilla of control hydropenic and furosemide-treated rats. The DVR plasma osmolality at the base, 573 +/- 40, rose to 1,011 +/- 118 mosmol/kg H2O at the tip in control animals but was 356 +/- 8 and 377 +/- 6, respectively in furosemide animals, demonstrating that the axial osmotic gradient was nearly eliminated. The DVR plasma protein concentration in control hydropenic rats was higher at the tip, 6.8 +/- 0.4 g/dl, than at the base, 5.2 g/dl (P less than 0.01), because of volume efflux from DVR between base and tip, but was 5.4 +/- 0.3 and 5.5 +/- 0.2 g/dl at the base and tip, respectively, in furosemide animals, indicating virtual abolition of volume efflux. In DVR at the tip in control animals, plasma protein concentration positively correlated with plasma osmolality (R = 0.72, P less than 0.02). These results support the hypothesis that transcapillary small-solute gradients influence transcapillary fluid movement in DVR.
View details for Web of Science ID A1989AV33000088
View details for PubMedID 2801959
INNER MEDULLARY BLOOD-FLOW IN POSTISCHEMIC ACUTE RENAL-FAILURE IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1989; 256 (3): F456-F461
To study the effect of renal ischemia on the circulation in the inner medulla, blood flow in descending and ascending vasa recta was determined by fluorescence videomicroscopy in the exposed papilla of the uninephrectomized rat after clamping of the renal artery for 45 min. Total renal blood flow was determined in parallel studies with an electromagnetic flowmeter. Animals were studied 90 min (group 1E) and 24 h (group 2E) after right nephrectomy and release of the left renal artery clamp. Control rats were studied 90 min (group 1C) and 24 h (group 2C) after right nephrectomy alone. In groups 1E and 2E, total renal blood flow was reduced to 70 and 80% of that in their respective controls; renal vascular resistance increased by 50 and 73%, respectively. In striking contrast, blood flow was markedly elevated in descending and ascending vasa recta in groups 1E and 2E compared with the values in their respective uninephrectomized controls. These results indicate that the circulation in the inner medulla is rapidly restored after 45 min of total renal ischemia and that vasa recta blood flow rises above normal after 90 min and 24 h, despite a reduction in total renal blood flow and an increase in renal vascular resistance.
View details for Web of Science ID A1989T693900086
View details for PubMedID 2923224
EFFECT OF URETERAL EXCISION ON INNER MEDULLARY SOLUTE CONCENTRATION IN RATS
AMERICAN JOURNAL OF PHYSIOLOGY
1988; 255 (6): F1225-F1229
To elucidate the role of the ureter in urinary concentration we studied the effect of partial and complete ureteral excision on urinary osmolality and papillary interstitial osmolality and on sodium, potassium, and urea concentrations in the antidiuretic rat. Urine and descending vasa recta (DVR) plasma samples were obtained by micropuncture of the left renal papilla before (period 1) and 45 min after (period 2) complete (group 1, n = 10 rats) or partial (group 2, n = 10 rats) ureteral excision. Urine osmolality fell from 2,063 +/- 156 (mean +/- SE) to 736 +/- 116 mosmol/kgH2O after complete ureteral excision (P less than 0.01). After partial ureteral excision, the fall was less than half as great, from 2,038 +/- 167 to 1,551 +/- 162 mosmol/kgH2O (P less than 0.01). Vasa recta plasma osmolality decreased from 1,742 +/- 133 to 860 +/- 119 mosmol/kgH2O after complete excision (P less than 0.01) but only from 1,830 +/- 146 to 1,504 +/- 154 mosmol/kgH2O after partial excision (P less than 0.05). Mean DVR plasma sodium concentration declined from 339 +/- 25 to 211 +/- 25 meq/l (P less than 0.01) in group 1 but did not change in group 2 (348 +/- 21 to 347 +/- 28 meq/l). The fraction of DVR plasma osmolality accounted for by urea decreased significantly from 0.59 +/- 0.01 to 0.46 +/- 0.02 mM/(mosmol/kgH2O) in group 1 and from 0.59 +/- 0.02 to 0.49 +/- 0.03 mM/(mosmol/kgH2O) for group 2 (P less than 0.01, both groups). We interpret these findings to show that the remnant ureter moderates the fall in interstitial osmolality at least in part through preservation of the corticomedullary sodium chloride gradient.
View details for Web of Science ID A1988R495800095
View details for PubMedID 3202184
EFFECTS OF INTRARENAL ADENOSINE ON RENAL-FUNCTION AND MEDULLARY BLOOD-FLOW IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1988; 255 (6): F1230-F1234
Adenosine is a potent vasodilator of the systemic circulation. Infusion of adenosine into the aorta causes water and sodium retention and a fall in glomerular filtration rate and renal blood flow. The effect of adenosine on medullary blood flow is unknown. Because systemic vasodilatory effects may confound its renal actions, adenosine was infused into the renal artery of anesthetized Munich-Wistar rats at doses of 2, 6, and 15 micrograms/min. A marked dose-dependent increase in urinary flow and sodium excretion was observed. Inulin and p-aminohippuric acid clearance did not change significantly. Blood flow in vasa recta in the exposed renal papilla, as determined by fluorescence videomicroscopy, increased significantly only with the highest dose of adenosine. In control animals infused with the vehicle only, there was no change in any of the above variables. These results indicate that direct intrarenal infusion of adenosine in the rat increases urinary flow and sodium excretion and at higher doses also increases vasa recta blood flow. The effects on urinary flow and sodium excretion were therefore mediated by a mechanism other than an increase in vasa recta blood flow.
View details for Web of Science ID A1988R495800096
View details for PubMedID 3202185
EFFECT OF LONG-TERM, ALTERNATE DAY FEEDING ON RENAL-FUNCTION IN AGING CONSCIOUS RATS
1988; 34 (5): 620-630
To examine the renal effects of lifelong intermittent feeding, we performed clearance and pathologic studies in 86 week old, awake male Sprague-Dawley rats fed on alternate days (N = 9) or ad libitum (N = 8) since the age of four weeks. Alternate day-fed rats were studied on both feeding and fasting days, and the values averaged. In the alternate day group the clearances of inulin (Cinulin) and PAH (CPAH), factored by body wt, were higher by 23% and 27%, respectively (P less than 0.05); albumin excretion (UalbV) was two orders of magnitude lower (P less than 0.001) and the percentage of glomeruli with lesions was eightfold lower (P less than 0.02) than in the ad libitum-fed group. The fractional clearances of neutral dextrans ranging in radii from 20 A to 42 A did not differ between the two groups. Compared to a previously published study of 30 week old, alternate day-fed rats, values for Cinulin and CPAH were similar while UalbV was higher (P less than 0.025) in the 86 week old alternate day-fed rats. Cinulin, however, was lower (P less than 0.005) while UalbV was much higher (P less than 0.001) in 86 week old, ad libitum-fed rats than in 30 week old, ad libitum-fed rats. The results indicate that long-term alternate day feeding preserves glomerular filtration rate (GFR) and renal plasma flow (RPF), while glomerular permselectivity is not completely preserved, as evidenced by an increase in microalbuminuria in aging awake male rats. Conversely, ad libitum feeding results in a significant decline in GFR and probably in RPF, in association with massive albuminuria and segmental glomerular sclerosis.
View details for Web of Science ID A1988Q582500004
View details for PubMedID 3199676
COURSE AND PATHOGENESIS OF POSTISCHEMIC ACUTE RENAL-FAILURE IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1988; 255 (2): F257-F264
The effect of 45-min clamping of the renal artery was studied in the conscious uninephrectomized rat to reproduce the syndrome of hemodynamically mediated acute renal failure in humans after a single ischemic insult. Twenty-four hours after ischemia, creatinine clearance was reduced by 90%, whereas fractional excretion of sodium was markedly increased; over the subsequent 5 days, both values returned to normal. The animals were nonoliguric. Fractional clearances of graded sizes of neutral dextrans (radii 20-44 A), employed to detect transtubular backleak of inulin, were not significantly different 24 or 48 h postischemia from those in normal animals. The implication that the normal fractional dextran clearances excluded tubular backleak was tested directly by microinjecting [methoxy-3H]inulin into the proximal tubule. In most tubules injected, the recovery of radioactivity in the urine was markedly lower 24 and 48 h postischemia than that in normal rats; in a few injected tubules of postischemic kidneys, recovery was not different from that in normal animals. The low recovery of radioactive inulin was accounted for, at least in part, by transtubular backleak, as shown in experiments in which rats subjected to renal ischemia were cross-transfused with normal animals. These studies indicate that, despite the normal fractional dextran clearances, most tubules were severely injured as shown by tubule backleak of inulin.
View details for Web of Science ID A1988P625900059
View details for PubMedID 2457326
UREA FLUX IN THE URETER
AMERICAN JOURNAL OF PHYSIOLOGY
1988; 255 (2): F244-F249
It has been hypothesized that urea from the final urine is recycled into the renal papilla through the pelvic epithelium. To test this hypothesis, samples of urine were collected by micropuncture proximally and distally through the intact, contracting ureter of the anesthetized rat. In 12 rats, in which urine flow was 5.89 +/- 0.67 microliter/min (a moderate antidiuresis), the ratio of proximal-to-distal urea concentration, corrected for water movement, was 0.93 +/- 0.03 (P less than 0.01 compared with unity), indicating that approximately 7% of urea in the urine emerging from the terminal collecting duct was reabsorbed by the time it reached the distal ureter. To assess the possible contribution of urea reabsorption by the ureter, the ureter was cannulated proximally and distally and perfused with urine of known composition at 6.26 +/- 0.10 microliter/min. In nine rats, the ratio of urea concentration in the perfusate collected from the distal end of the ureter to that in the perfusate entering the proximal end was 0.93 +/- 0.02 (P less than 0.01 compared with unity), indicating 7% reabsorption. Movement of solute across the ureteral epithelium was not restricted to urea. Potassium and creatinine were also reabsorbed [3.4 +/- 0.9 (P less than 0.01) and 3.5 +/- 1.2% (P less than 0.05), respectively], whereas sodium was secreted [9.2 +/- 2.3% (P less than 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1988P625900057
View details for PubMedID 3407782
MICROPUNCTURE STUDY OF THE EFFECT OF ANP ON THE PAPILLARY COLLECTING DUCT IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1988; 254 (4): F477-F483
Micropuncture collections were obtained from the terminal collecting duct (CD) at base and tip of the renal papilla of the rat. Group 1 was studied before and during infusion with atrial natriuretic peptide (ANP), group 2 was administered the vehicle only, and group 3 received acetazolamide to increase sodium delivery to the base to a similar extent as after ANP. ANP caused a decrease in blood pressure, a slight increase in GFR, natriuresis, and diuresis. Sodium delivery to the collecting duct at the base of the papilla increased. Between base and tip, sodium reabsorption was inhibited. Tubule fluid sodium concentration (TFNa) was increased at the base and remained high at the tip; in contrast TFNa fell between base and tip in control and acetazolamide groups. After acetazolamide, sodium reabsorption in the terminal CD was not inhibited. These results demonstrate that in vivo ANP 1) increases the delivery of sodium to the terminal CD and 2) inhibits sodium reabsorption in the terminal CD. The findings for chloride were similar to those for sodium. ANP also increased delivery of H2O, K, Ca, and Mg to the CD at the papillary base but did not significantly affect their transport by the terminal CD.
View details for Web of Science ID A1988N029100058
View details for PubMedID 2965515
THE EFFECT OF INTRARENAL ADENOSINE ON RENAL EXCRETORY FUNCTION AND HEMODYNAMICS IN THE RAT
SLACK INC. 1988: A627–A627
View details for Web of Science ID A1988M818002217
HORMONE RECEPTOR INTERACTIONS - DISCUSSION
1987; 32: S61-S67
View details for Web of Science ID A1987L382100009
MEMBRANE TRAFFIC IN MDCK CELLS - DISCUSSION
1987; 32: S208-S210
View details for Web of Science ID A1987L382100029
EFFECT OF ADRENALECTOMY ON TRANSPORT IN THE RAT MEDULLARY THICK ASCENDING LIMB
JOURNAL OF CLINICAL INVESTIGATION
1987; 80 (4): 1160-1164
Previous studies in adrenalectomized (Adx) rats suggest that aldosterone may regulate ion transport in the ascending portion of Helen's loop. In order to examine directly the effect of adrenalectomy on transport, medullary thick ascending limb (Mtal) segments were isolated from Adx, Adx replaced with aldosterone (Adx + Ald, 0.5 micrograms X 100 g X body wt X d), and control Sprague-Dawley rats. Both net sodium and net chloride fluxes were significantly less in the Mtal segments from Adx rats compared with those in the control or Adx + Ald group. Physiologic levels of exogenous aldosterone increased net sodium chloride flux toward control values in the Adx + Ald group. Net potassium flux was not different among the three groups. We conclude that adrenalectomy impairs reabsorptive NaCl but not K transport in the Mtal, and that aldosterone restores this process. This reabsorptive defect may contribute to the urinary concentrating and diluting abnormality associated with adrenal insufficiency.
View details for Web of Science ID A1987K340400034
View details for PubMedID 3654975
EFFECT OF V2-RECEPTOR-MEDIATED CHANGES ON INNER MEDULLARY BLOOD-FLOW INDUCED BY AVP
AMERICAN JOURNAL OF PHYSIOLOGY
1987; 253 (3): F576-F581
We have previously shown that arginine vasopressin (AVP) in physiological amounts reduces inner medullary blood flow and that the mechanism of this decrease is at least in part mediated by the vasopressor (V1-receptor) action of AVP. To determine whether the antidiuretic action of AVP (V2-receptor) also contributes to the reduction in inner medullary blood flow, we determined capillary blood flow (QVR) in individual descending vasa recta (DVR) and ascending vasa recta (AVR) using fluorescence videomicroscopy in the exposed renal papilla of the anesthetized rat. Three groups of chronically water-diuretic rats were studied in three consecutive periods: control (period 1), experimental (period 2), and recovery (period 3). Group I rats (designated the AVP group) received AVP, 45 ng X h-1 X kg body wt-1; group II (AVP + V2-inhibitor), AVP plus its specific antidiuretic antagonist d(CH2)5[D-Ile2,Thr4]AVP; and group III (V2-inhibitor), the antagonist alone, respectively, in the experimental period 2. Only group I rats concentrated their urine, urine osmolality (Uosmol) = 499 +/- 48 mosmol/kgH2O, whereas urine remained hypotonic throughout in groups II and III. In group I, QVR in DVR and AVR decreased in period 2; but in groups II and III, QVR tended to increase. These results suggest that the AVP-induced decrease in papillary vasa recta blood flow is in part mediated by its antidiuretic V2-receptor as well as by its vasopressor (V1-receptor). They also suggest that the rate of urinary flow in the medullary collecting ducts is a determinant of inner medullary blood flow.
View details for Web of Science ID A1987K521200075
View details for PubMedID 2957929
THE RENAL CONCENTRATING MECHANISM
1987; 32: S43-S50
View details for Web of Science ID A1987J355400008
EFFECT OF ATRIAL-NATRIURETIC-PEPTIDE ON VASA RECTA BLOOD-FLOW IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1987; 252 (6): F1112-F1117
To determine whether synthetic atrial natriuretic peptide (ANP) increases renal medullary blood flow and if so whether the increase mediates the diuresis and natriuresis induced by ANP, inner medullary vasa recta blood flow in the exposed left renal papilla of anesthetized Munich Wistar rats weighing between 102 and 161 g was measured by fluorescence videomicroscopy. The rats were maintained in a euvolemic state by the infusion of albumin. Synthetic ANP (Auriculin B) was administered intravenously as 2.5 micrograms/kg body wt prime and as a continuous infusion of 0.2 microgram X min-1 X kg body wt-1 to the experimental group (n = 7). Within 2 min after ANP was given, urine flow and sodium excretion increased (29.4 +/- 3.8 to 50.4 +/- 5.8 microliter X min-1 X kidney wt-1, P less than 0.01, and 3.39 +/- 0.57 to 6.05 +/- 0.95 mueq X min-1 X g kidney wt-1, P less than 0.01, respectively), but vasa recta blood flow in descending (DVR) or ascending (AVR) vasa recta did not change significantly (9.5 +/- 2.3 to 10.0 +/- 2.8 nl/min in DVR and 5.3 +/- 1.0 to 6.1 +/- 1.2 nl/min in AVR). Forty-five minutes after ANP was begun, urine flow and sodium excretion increased further (77.1 +/- 11.1 microliter X min-1 X g kidney wt-1 and 12.0 +/- 2.15 mueq X min-1 X g kidney wt-1, respectively), and by this time vasa recta blood flow had increased significantly to 14.0 +/- 2.6 in DVR, P less than 0.01, and 9.8 +/- 1.2 in AVR, P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1987H804100074
View details for PubMedID 2954471
- POTASSIUM RECYCLING KIDNEY INTERNATIONAL 1987; 31 (3): 695-703
- TRIBUTE TO BERLINER,ROBERT KIDNEY INTERNATIONAL 1987; 31 (2): 502-506
THE MEDULLARY MICROCIRCULATION
1987; 31 (2): 641-647
Like other regional circulations, the medullary circulation supplies oxygen and other primary substrates to the medulla and removes carbon dioxide and other waste metabolites. It also acts as a countercurrent exchanger and simultaneously removes water reabsorbed from the renal tubule to preserve mass balance. Our present understanding of how the medulla serves both these functions at the same time is illustrated in Figure 3. Blood leaves the efferent arteriole with an elevated plasma protein concentration as a consequence of glomerular filtration, and flows down descending vasa recta within a vascular bundle. The increased interstitial osmotic-concentration coupled with a finite capillary reflection coefficient for small solutes causes additional water to be extracted so that at the termination of descending vasa recta, the plasma protein concentration exceeds that in the systemic circulation by approximately twofold. Solute, urea more than sodium chloride, also enters descending vasa recta. As blood flows through the interconnecting capillary plexus and up ascending vasa recta, transcapillary oncotic and osmotic pressure differences combine to cause capillary uptake of fluid. There is also simultaneous loss of urea such that the medullary trapping of urea is very effective. Countercurrent exchange of sodium chloride, however, appears to be less efficient and as a consequence, not only water but sodium chloride is removed from the medulla. Antidiuretic hormone reduces medullary blood flow, both directly by its vasoconstrictor (V1-receptor mediated) effect and indirectly by its antidiuretic (V2-receptor mediated) effects. Prostaglandins are able to enhance medullary blood flow by counteracting vasoconstrictive influences.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1987F981500020
View details for PubMedID 3550235
SHORT AND LONG LOOP NEPHRONS
1987; 31 (2): 597-605
The explanation for the necessity to have both short and long loop nephrons for urinary concentration is unknown but may represent nature's resolution of conflicting ideal conditions for maximum urinary concentration. Ideally, one would like the thick ascending limb to extend throughout the entire medulla to the papillary tip and be supplied by a blood flow vigorous enough to provide oxygen and remove waste products as rapidly as needed. One would also like to have a progressively smaller volume of tissue to be concentrated toward the papillary tip to lessen the osmotic work required and a highly efficient vascular exchange system to sequester the medullary interstitial solute effectively. But the same efficiency of countercurrent exchange of oxygen causes the inner medulla to have a relatively low oxygen content. The presence of the thin loops of Henle in the inner medulla may represent a compromise between these conflicting ideals. The papilla tapers to a low mass, which allows a mechanism requiring only a modest energy supply to increase the tonicity of the interstitium enormously. The reduced work requirement obivates the need for thick ascending limbs to extend into the papilla where they would be highly vulnerable to anoxia. The outer medulla with its larger mass and thick ascending limbs supplied by a high blood flow can initiate the operation to reduce the volume of fluid and solute to be concentrated, and at the same time carry out other functions required of the filtration-reabsorption kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1987F981500014
View details for PubMedID 3550229
CURRENT TOPICS IN MEMBRANES AND TRANSPORT
1987; 28: 115-131
View details for Web of Science ID A1987M184700007
THE SHAPE OF RENAL VASA RECTA CAPILLARIES AND ITS EFFECT ON CALCULATION OF SINGLE CAPILLARY BLOOD-FLOW
1986; 32 (1): 1-20
Previous studies of the renal papilla of the rat have suggested that the vasa recta capillaries can be well approximated by elliptical cylinders (C. Holliger, K. V. Lemley, S. L. Schmitt, F. C. Thomas, C. R. Robertson, and R. L. Jamison, 1983, Circ. Res., 53, 401-413). This hypothesis was validated in a morphological study employing several methods of specimen fixation and preparation. Papillas of young (body wt = 90 g) Wistar rats were fixed and subsequently examined by light and electron microscopy. Cross-sectional shapes and orientations were determined for 300 superficial vasa recta. The ratio, beta, of vessel cross-sectional major-axis-to-minor-axis lengths was 1.39 +/- 0.24 (SD). Values of beta greater than 1.0 (the value expected for circular vessels) could not be accounted for by either fixation artifact or the angle of histologic sectioning of the papillas. A quantitative estimate of the relationship between the apparent capillary diameter measured in vivo and the capillary cross-sectional area was made using a mathematical model which accounts for cross-sectional shapes and orientations of the vasa recta. This estimate implies that current methods of calculating single vas rectum blood flow using apparent diameters and blood velocities determined in vivo probably overestimate actual blood flow by about 25%.
View details for Web of Science ID A1986D032900001
View details for PubMedID 3736443
EFFECT OF INTERMITTENT FEEDING ON RENAL HEMODYNAMICS IN CONSCIOUS RATS
AMERICAN JOURNAL OF PHYSIOLOGY
1986; 250 (3): F566-F572
The hemodynamic influences of many forms of dietary restriction have not been studied in the conscious rat. To examine the effect of one regimen of dietary restriction, alternate-day feeding, on renal hemodynamics, we performed 56 clearance studies in 20 unanesthetized, previously catheterized male Sprague-Dawley rats at mean age 30 wk. Group 1 rats (n = 10) were given standard chow only on alternate days for 25 wk and then studied after feeding and after fasting days, whereas group 2 rats (n = 10) were fed ad libitum during the same period and then studied randomly. In group 1, glomerular filtration rate (GFR, clearance of inulin) and renal blood flow [RBF, clearance of PAH/(1 - hematocrit)] increased 23 and 19%, respectively, after feeding days compared with fasting days (GFR, 4.25 vs. 3.47 ml/min, P less than 0.005; RBF, 22.2 vs. 18.6 ml/min, P less than 0.025). After feeding, mean arterial pressure and plasma protein concentration were unchanged, hematocrit increased slightly, and fractional excretion of sodium rose from 0.23 to 0.57%. Both GFR and RBF averaged 31% less in group 1 than in group 2 but, when factored by body weight, the differences were abolished. The results indicate that alternate-day feeding causes substantial oscillations in GFR and RBF in healthy awake rats through mechanisms unlikely to involve changes in extracellular fluid volume alone and limits GFR and RBF to average values markedly lower than those observed for larger ad libitum-fed rats of the same age.
View details for Web of Science ID A1986A526900082
View details for PubMedID 3953831
ROLE OF V2 RECEPTOR IN ARGININE VASOPRESSIN (AVP) EFFECT ON VASA RECTA BLOOD-FLOW
NATURE PUBLISHING GROUP. 1986: 418–18
View details for Web of Science ID A1986AXU3601070
- THE MICROCIRCULATION OF THE RENAL MEDULLA CIRCULATION RESEARCH 1985; 57 (5): 657-667
EFFECT OF ARGININE VASOPRESSIN (AVP) ON VASA RECTA BLOOD-FLOW
NATURE PUBLISHING GROUP. 1985: 302–
View details for Web of Science ID A1985ABK7500839
USE OF DIGITAL CROSS-CORRELATION FOR ONLINE DETERMINATION OF SINGLE-VESSEL BLOOD-FLOW IN THE MAMMALIAN KIDNEY
1985; 30 (1): 63-74
The empirical relationship between erythrocyte velocity (Vrbc) and mean blood velocity (Vblood) was studied in quartz capillaries by television microscopy using the dual-slit technique. A newly designed desktop digital on-line cross-correlator was combined with a computer to determine Vrbc. The accuracy of the digital correlator was tested for velocities ranging from 0 to 3 mm/sec and compared with values determined using an analog tracking correlation device. There was good agreement. Small-bore glass tubes with diameters ranging from 12 to 26 micron were perfused with suspensions of erythrocytes having hematocrits between 10 and 37%. The relationship between mean blood velocity and erythrocyte velocity in these quartz tubes was found to be Vblood = 0.88 Vrbc - 0.11, and was independent of diameter and hematocrit within the range investigated. The mean ratio for Vrbc/Vblood was 1.42 +/- 0.06.
View details for Web of Science ID A1985ALE3700007
View details for PubMedID 4021838
FLUID UPTAKE IN THE RENAL PAPILLA BY VASA RECTA ESTIMATED BY 2 METHODS SIMULTANEOUSLY
AMERICAN JOURNAL OF PHYSIOLOGY
1985; 248 (3): F347-F353
Fluid uptake by vasa recta was determined by two independent methods, videomicroscopy and the micropuncture technique, in the exposed papilla of nine antidiuretic rats to reconcile differences in values previously obtained by the two techniques. Erythrocyte velocity (Vrbc) and diameter (D) in descending vasa recta (DVR) (n = 22) and ascending vasa recta (AVR) (n = 31) near the "base" of the papilla were measured. Using a conversion function determined in vitro, Vrbc was transformed into mean blood velocity (Vblood). From D and Vblood, mean blood flow (Q) in DVR and AVR was calculated. In DVR, mean Vrbc, D, and Q were 1.06 +/- 0.01 mm/s, 16.3 +/- 0.4 micron, and 10.6 +/- 1.4 nl/min, respectively. In AVR, each corresponding value differed significantly, 0.47 +/- 0.06 mm/s (P less than 0.001), 19.8 +/- 0.8 micron (P less than 0.001), and 5.65 +/- 1.3 nl/min (P less than 0.025), respectively. Blood samples from DVR and AVR were obtained by micropuncture from the same location. Plasma protein concentration (g/dl) was 5.1 +/- 0.6 in DVR, 4.0 +/- 0.4 (P less than 0.05) in AVR, and 3.6 +/- 0.3 (P less than 0.025) in the renal vein. Assuming no net transcapillary loss of protein, total plasma outflow exceeded inflow by 29%, the excess representing fluid uptake; and to reconcile the blood flow and plasma protein concentrations found, functioning AVR should outnumber functioning DVR by a ratio of 2.1-2.4 to 1, depending on local hematocrit. Given the total number of AVR + DVR = 2,944 (at the base), capillary fluid uptake was calculated to range between 1.5 and 2.6 microliter/min.
View details for Web of Science ID A1985ADR5100037
View details for PubMedID 3976897
THE VARIABLE HYPONATREMIC RESPONSE TO HYPERGLYCEMIA
WESTERN JOURNAL OF MEDICINE
1985; 142 (1): 49-53
Hyperglycemia may lower the plasma sodium concentration. Theoretical analyses have suggested that elevations in glucose concentration produce an invariant hyponatremic response. We propose, however, that change in plasma sodium concentration in response to hyperglycemia is variable and depends on (1) the distribution of total body water and solute, (2) the relationship between the gain of extracellular glucose and the loss of intracellular solute and (3) the intake and loss of solute and water. These factors are incorporated into a formulation of the relationship between the plasma sodium and glucose concentrations.
View details for Web of Science ID A1985AKL4700004
View details for PubMedID 3976219
EFFECT OF ACUTE POTASSIUM LOAD ON REABSORPTION IN HENLES LOOP IN CHRONIC RENAL-FAILURE IN THE RAT
1985; 27 (6): 919-927
To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and after (period 2) acute loads of potassium chloride (KCl group), equimolar sodium chloride (NaCl group) or no solute (time control). The KCl load increased urinary potassium excretion to a greater extent (from 5 to 50%, P less than 0.005) than in NaCl (14 to 27%) or time control (9 to 14%), and caused as great a diuresis and natriuresis as did NaCl. Fractional delivery of water, sodium, and potassium to the end-proximal tubule increased similarly in the NaCl and KCl groups and slightly less so in the time control group in period 2. The major finding was a striking increase in potassium delivery to the beginning of the distal tubule (from 17 to 37%) in period 2 which was substantially greater than in the combined control groups (13 to 19%, P less than 0.025) and was equivalent to three-quarters of urinary potassium excretion. This was the consequence of an increase in the filtered load of potassium, an increase in absolute delivery of potassium from the proximal tubule (P less than 0.005), and a decrease in fractional potassium reabsorption by the loop of Henle from 64 to 48%, versus 72 to 69% in the control groups (P less than 0.01). These results suggest that the proximal tubule and, in particular, Henle's loop play a role in excreting an acute potassium load in chronic renal failure.
View details for Web of Science ID A1985ALK2100012
View details for PubMedID 4021320
VIDEOMICROSCOPIC METHOD FOR DIRECT DETERMINATION OF BLOOD-FLOW TO THE PAPILLA OF THE KIDNEY
ANNALS OF BIOMEDICAL ENGINEERING
1985; 13 (3-4): 273-280
We adapted the technique of videomicroscopy for direct determination of blood flow in individual capillaries of the papilla of the kidney, the ascending vasa recta (AVR) and descending vasa recta (DVR). The papilla was exposed in anesthetized rats and positioned under a video-camera-microscope and viewed under epiillumination. The intravenous infusion of fluorescein-isothiocyanate (FITC)-labeled gamma globulin was combined with fluorescence microscopy to enhance the contrast among plasma, red blood cells and capillary walls. On the television monitor, the walls were clearly outlined, enabling the measurement of capillary diameter. The velocity of red cells (Vrbc) in individual vasa recta was measured using the dual slit technique. From the videotape recorded microscopic image of a vas rectum, two photometric signals were obtained by integrating the light intensity from two electronic "windows" positioned closely together over the same capillary. Red cell velocity was calculated by dividing the distance between the two windows by the time delay between signals. The delay was determined using analog correlation tracking or digital cross correlation techniques. Single vasa recta blood flow was calculated from capillary diameter, Vrbc, and F (Fahraeus factor), which converts Vrbc to average whole blood velocity, Vblood. In quartz capillaries the same size as vasa recta, the ratio F = Vrbc/Vblood = 1.42 +/- 0.06. Total papillary blood inflow and outflow was calculated by multiplying the total number of DVR or AVR times the mean single capillary blood flow for DVR or AVR, respectively.
View details for Web of Science ID A1985AMX8400006
View details for PubMedID 4037456
EFFECT OF ARGININE VASOPRESSIN ON RENAL MEDULLARY BLOOD-FLOW - A VIDEOMICROSCOPIC STUDY IN THE RAT
JOURNAL OF CLINICAL INVESTIGATION
1985; 76 (2): 770-778
The role of arginine vasopressin (AVP) in the regulation of renal medullary blood flow is uncertain. To determine if AVP has a direct vasoconstrictive action on vasa recta, the effect of AVP on erythrocyte velocity (VRBC), diameter, and blood flow (QVR) in descending vasa recta (DVR) and ascending vasa recta (AVR) was studied in the exposed renal papilla of four groups of chronically water diuretic rats using fluorescence videomicroscopy. There were three periods: control (period 1), experimental (period 2), and recovery (period 3). In periods 1 and 3, all groups received hypotonic saline. In period 2, group I rats (AVP) received AVP (45 ng/h per kg body wt); group II (time) received hypotonic saline alone; group III (AVP plus V1-inhibitor) received AVP plus its vascular antagonist, d(CH2)5Tyr(Me)AVP; and group IV (V1-inhibitor) received the vascular antagonist alone. Another group of rats (group V) was employed to demonstrate that the rise in blood pressure induced by a 3- or 10-ng/kg injection of AVP was virtually abolished by the prior infusion of the V1-inhibitor. The urine of group III as well as group I rats was concentrated (Uosm = 721 +/- 62 H2O vs. 670 +/- 39 mosM/kg), while urine remained dilute in groups II and IV. In period 2, VRBC and QVR in DVR and AVR decreased in group I, did not decrease in group III, and increased in groups II and IV. The vascular antagonist thus completely abolished the AVP-induced decrease in QVR in group III. These findings unequivocally establish that AVP in physiological amounts reduces medullary blood flow, at least in part, by a direct vasoconstrictive action on the medullary microcirculation. They also show that an effect of AVP on medullary blood flow is not necessary for its antidiuretic effect.
View details for Web of Science ID A1985APT9300051
View details for PubMedID 4031072
PROSTAGLANDIN SYNTHESIS INHIBITORS AND VASA RECTA ERYTHROCYTE VELOCITIES IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1984; 247 (4): F562-F567
Vasa recta erythrocyte velocities (VRBC) in the exposed renal papilla of anesthetized water-loaded rats were determined before and 60 min after intravenous administration of a prostaglandin synthesis inhibitor (indomethacin, meclofenamate) or the inhibitor vehicle alone. The change in VRBC of ascending and descending vasa recta for the inhibitor group [-17 +/- 5% (SE)] was different from that for controls (+12 +/- 4%, P less than 0.002). Erythrocyte velocities were also determined in vasa recta of antidiuretic rats before and 30 min after administration of indomethacin or vehicle alone. Prostaglandin synthesis inhibition was again associated with a significant decrease in VRBC compared with control (-24 +/- 4% vs. +28 +/- 20%, respectively, P less than 0.025). These findings suggest that prostaglandins play a similar role in regulating blood flow in the renal medulla in water diuresis and antidiuresis.
View details for Web of Science ID A1984AAJ2100052
View details for PubMedID 6496683
DIGITAL CROSS-CORRELATION FOR ONLINE DETERMINATION OF SINGLE VESSEL BLOOD-FLOW IN THE MAMMALIAN KIDNEY IN EPI-ILLUMINATION
KARGER. 1984: 537–37
View details for Web of Science ID A1984TH32700530
STRUCTURE AND FUNCTION OF THE RENAL PAPILLA
SEMINARS IN NEPHROLOGY
1984; 4 (1): 5-26
View details for Web of Science ID A1984SH51900003
EXAMINATION OF TRANS-EPITHELIAL EXCHANGE OF WATER AND SOLUTE IN THE RAT RENAL PELVIS
JOURNAL OF CLINICAL INVESTIGATION
1984; 74 (5): 1860-1870
Severance of the ureter beyond the renal papilla causes a fall in urinary osmolality, which suggests that exchange of water or solute between urine and renal parenchyma normally occurs in the intact renal pelvis. We examined water and solute flux in the renal pelvis with micropuncture and microcatheterization techniques. Four groups of antidiuretic rats were studied. Group I (n = 17) underwent micropuncture through the intact contracting ureter. Urine samples were obtained at the papillary tip, and in the pelvis beside the base of the extrarenal papilla. Urinary osmolality at the base, 880 +/- 97 mosmol/kg H2O (mean +/- SE), was less than that at the tip, 1,425 +/- 104 mosmol/kg H2O (P less than 0.005). In group II (n = 24), samples were analyzed for inulin and osmolality. In 15 rats (group IIA), comparison was made between base and tip samples. In the other nine animals (group IIB), comparisons were made among base, tip, and bladder samples and urea was also measured. In group II (A and B combined) urine-to-plasma (U/P) osmolality was lower at the base, 4.31 +/- 0.27, than at the tip, 6.08 +/- 0.23 (P less than 0.001), and U/P inulin was lower at the base, 192 +/- 25, than at the tip, 306 +/- 16 (P less than 0.001). In group IIB, the bladder urine had a lower U/P osmolality, 5.27 +/- 0.25, than the tip, 6.01 +/- 0.31 (P less than 0.02). The U/P urea was 59 +/- 10.6 (base), 98 +/- 9.4 (tip) (base vs. tip, P less than 0.05), and 81 +/- 6.5 (bladder, P less than 0.005, compared with tip). In group III (n = 8), samples were obtained by microcatheter from the fornices, the deepest intrarenal extensions of the pelvis, and compared with samples at the tip. Urinary osmolality was lower in the fornix, 646 +/- 106 mosmol/kg H2O, than at the tip, 1,296 +/- 99 mosmol/kg H2O (P less than 0.001). Similarly, U/P inulin was lower in the fornix, 48 +/- 14, than at the tip, 128 +/- 12 (P less than 0.001). The lower U/P inulin in the pelvic urine is the result of either the addition of fluid to the pelvis, or the backleak of inulin across the epithelium lining the pelvis. To verify that the pelvic epithelium was impermeable to inulin, in group IVA (n = 4) the left renal pelvis was superfused with a solution of chemical inulin. Cumulative absorption of inulin from the left kidney was 0.15 +/- 0.08% of that superfused. Using [14C]inulin in group IVB (n= 3), similar results were obtained (0.05 +/- 0.02%). These findings indicate that in the renal pelvis, fluid is added to urine after it emerges from the collecting ducts. We suggest that reflux of hyperosmotic urine over the renal papilla creates a transepithelial gradient for the flux of water into the pelvis. A model that incorporates diffusive and convective forces for water and solute transport is proposed to account for these findings.
View details for Web of Science ID A1984TS19400035
View details for PubMedID 6501575
- A PATIENT WITH POLYURIA AND HYPONATREMIA KIDNEY INTERNATIONAL 1983; 24 (2): 256-267
DETERMINATION OF BLOOD-FLOW IN THE RENAL PAPILLA BY DIRECT TELEVISION MICROSCOPY
BLACKWELL SCIENCE INC. 1983: 622–22
View details for Web of Science ID A1983TL40000017
DIRECT DETERMINATION OF RENAL PAPILLARY BLOOD-FLOW
NATURE PUBLISHING GROUP. 1983: 245–45
View details for Web of Science ID A1983PY31500622
EFFECT OF ACUTE POTASSIUM LOAD ON REABSORPTION IN HENLE LOOP IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1983; 245 (5): F569-F576
Rats fed a low potassium diet were studied before and after KCl infusion to determine whether potassium recycling in the renal medulla accelerates potassium excretion by increasing delivery of sodium, water, and potassium to the distal tubule. Fluid samples were obtained from the end-proximal and beginning-distal tubule before and at the same sites after KCl loading by re-collection micropuncture and were compared with samples obtained from similarly fed control animals not infused with KCl. Potassium excretion increased in the KCl group from 3 to 48% but remained low in the controls. Fractional sodium and water delivery to end-proximal and beginning-distal tubule increased with time equally in both groups. Potassium reabsorption in Henle's loop fell from 75 to 58% (P less than 0.005) after KCl infusion but not significantly in the controls (from 77 to 75%). Fractional potassium delivery to the distal tubule increased from 12 to 26% (P less than 0.005) in the KCl group, which could account for over half the potassium excreted. The increase in controls from 12 to 17% was significantly less (P less than 0.02). These findings suggest that potassium recycling reduces potassium reabsorption in Henle's loop, enabling the loop to participate with the distal and collecting tubule in accelerating urinary excretion of an acute potassium load.
View details for Web of Science ID A1983RR32700106
View details for PubMedID 6638178
DIRECT DETERMINATION OF VASA RECTA BLOOD-FLOW IN THE RAT RENAL PAPILLA
1983; 53 (3): 401-413
Blood flow in vasa recta capillaries of the exposed renal papilla of young antidiuretic rats (n = 18) was determined by an adaptation of the video-photometric technique of Intaglietta. The erythrocyte velocity and capillary diameter in vasa recta (n = 97) were measured at the same location by means of fluorescence video microscopy, with fluorescein-labeled bovine gamma-globulin as a plasma marker. A factor relating erythrocyte velocity to mean cross-sectional blood velocity was determined in vitro to permit the calculation of single vasa recta blood flows from the measured indices, erythrocyte velocity and capillary diameter. Mean blood flow in descending vasa recta was 8.83 +/- 0.96 (SE) nl/min, significantly greater than that in ascending vasa recta, 4.82 +/- 0.34 nl/min. The total numbers of ascending and descending vasa recta at the base of the exposed papilla were also determined. Over 1500 vasa recta were identified as ascending vasa recta or descending vasa recta in electron micrographs of three papillas. At this level in the papilla (2 mm from the tip), there were four ascending vasa recta for each descending vas rectum. From the total numbers of ascending vasa recta and descending vas rectum, single vessel blood flows were converted to total blood flow. Total blood outflow in all ascending vasa recta, 11.3 microliter/min, substantially exceeded total blood inflow in all descending vasa recta, 5.2 microliter/min. The difference between outflow and inflow (6.1 microliter/min) represents an estimate of water by the papillary microcirculation, and is more than adequate to accommodate the known rate of water reabsorption from the collecting ducts of the exposed papilla.
View details for Web of Science ID A1983RH49300012
View details for PubMedID 6883657
THE RENAL CONCENTRATING MECHANISM - MICROPUNCTURE STUDIES OF THE RENAL MEDULLA
1983; 42 (8): 2392-2397
Micropuncture of the rat renal papilla has disclosed an outward transepithelial gradient for NaCl at the bend of Henle's thin loop and an electrical potential difference, lumen positive, in the ascending thin limb. Substantial water extraction and urea secretion occur somewhere proximal to the bend, but direct evidence for transepithelial NaCl movement across the rat descending thin limb is lacking. In the hamster, water is extracted and urea secreted, but no NaCl gradient has been found, and in Psammomys there is indirect evidence for transepithelial entry of NaCl into the descending limb. Fluid is diluted in the ascending thin limb by reabsorption of NaCl. The lack of unequivocal evidence for active NaCl reabsorption has stimulated a search for alternative mechanisms of osmotic work in the inner medulla. The collecting duct plays a crucial role by its differential reabsorption of water (primarily in the cortex) and urea (exclusively in the inner medulla) but has not yet been shown to supply useful energy to the concentrating mechanism by active sodium reabsorption. Exposure of the papillary tip by ureteral excision impairs urinary osmolality. Ureteral peristalsis normally causes intermittent flow of fluid in the collecting duct, but abolition of intermittent flow by paralysis of the ureter does not decrease urinary osmolality. Superperfusion of the exposed papilla by a urea solution prevents the decline in osmolality but the amount of urea used greatly exceeds that available from the urine. Nevertheless, it is the intactness of the ureter that is somehow essential to maximum urinary concentration, perhaps by preventing loss of solute from the papilla rather than by supplying energy.
View details for Web of Science ID A1983QR09500005
View details for PubMedID 6341087
- DIETARY-PROTEIN, GLOMERULAR HYPEREMIA, AND PROGRESSIVE RENAL-FAILURE ANNALS OF INTERNAL MEDICINE 1983; 99 (6): 849-851
SURREPTITIOUS DIURETIC INGESTION AND PSEUDO-BARTTERS SYNDROME
AMERICAN JOURNAL OF MEDICINE
1982; 73 (1): 142-147
A patient with profound hypokalemia satisfied the criteria for Bartter's syndrome, including hyperreninemia, aldosteronism, normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. Two screening tests of urine and one of plasma for diuretic agents gave negative results. A third urinary sample gave negative results for thiazide but positive for furosemide; the fourth and fifth samples gave negative results for furosemide but positive for thiazide. Urinary prostaglandin excretion was normal. We conclude that this apparent case of Bartter's syndrome was caused by long term surreptitious diuretic ingestion and suggest this may occur more frequently than is generally appreciated.
View details for Web of Science ID A1982NY22700020
View details for PubMedID 7091169
VASA RECTA BLOOD-FLOW - DETERMINATION OF FLOW PARAMETERS
FEDERATION AMER SOC EXP BIOL. 1982: R10–R10
View details for Web of Science ID A1982NG28200016
EFFECTS OF ACUTE ACID-BASE DISTURBANCES ON RENAL TUBULE REABSORPTION OF MAGNESIUM IN THE RAT
AMERICAN JOURNAL OF PHYSIOLOGY
1982; 243 (2): F197-F203
The effects of acute metabolic and respiratory acidosis and acute metabolic alkalosis on magnesium excretion and on fractional magnesium delivery to the end-accessible proximal tubule of the superficial nephron and the end-descending limb of the juxtamedullary nephron were examined by micropuncture in anesthetized thyroparathyroid-intact rats. Compared with normal control rats, acute metabolic acidosis (HCl infusion) did not produce any significant change. Acute respiratory acidosis (15% CO2 in inspired air) significantly increased the absolute but not the fractional excretion of magnesium and did not alter fractional delivery of magnesium to the end-accessible superficial proximal tubule or juxtamedullary end-descending limb. Acute metabolic alkalosis (NaHCO3 infusion) significantly reduced absolute and fractional magnesium excretion and fractional magnesium delivery to the end-descending limb of the juxtamedullary nephron but did not affect fractional magnesium delivery to the end-accessible proximal tubule of the superficial nephron. Tubule fluid-to-ultrafilterable magnesium ratio was a function of tubule fluid-to-plasma inulin ratio in the end-descending limb when all groups were combined. These results suggest that although acute metabolic or respiratory acidosis has no significant effect, acute metabolic alkalosis enhances magnesium reabsorption in the juxtamedullary proximal nephron--possibly in the pars recta.
View details for Web of Science ID A1982PC51800062
View details for PubMedID 7114219
DISORDERS OF URINARY CONCENTRATION AND DILUTION
AMERICAN JOURNAL OF MEDICINE
1982; 72 (2): 308-322
A new approach to the classification of disorders of urinary concentration and dilution is recommended based on recent studies of how the kidney elaborates a urine of widely varying osmolality. The capacity to concentrate urine depends on ft, the fractional reabsorption of solute delivered to the loop of Henle; fu, the excretion of solute relative to the sum of solute excretion and solute delivery to Henle's loop; fw, the fraction of solute loss by vascular outflow from the medulla relative to that reabsorbed by the loop; and finally, collecting duct response to antidiuretic hormone (ADH). A decrease in ft or in increased fu or fw will diminish urinary concentrating ability, as will resistance of the tubule to ADH. Conversely, urinary dilution depends on the delivery of sodium and water to the ascending limb; NaCl reabsorption by the ascending limb; and the absence of ADH. A decrease in sodium and water delivery to the ascending limb or in NaCl reabsorption by the ascending limb will impair urinary diluting ability, as will the presence of ADH. The consequences of disorders in urinary concentrating and diluting ability vary widely. In an alert patient with an intact thirst center, there may be no consequence; in a patient unable to communicate thirst or whose thirst center is deranged, the results may be catastrophic. Keeping in mind the kidney's few basic requirements for formation of concentrated or dilute urine may help the physician avoid these potentially serious dislocations of water balance.
View details for Web of Science ID A1982NB85700018
View details for PubMedID 7036728
URINARY CONCENTRATION IN THE PAPILLARY COLLECTING DUCT OF THE RAT - ROLE OF THE URETER
JOURNAL OF CLINICAL INVESTIGATION
1982; 69 (1): 157-164
Urine was observed to flow intermittently in the collecting ducts of the extrarenal papilla of antidiuretic rats. The purpose of this investigation was to test Reinking and Schmidt-Nielsen's hypothesis that intermittent flow plays an important role in the production of maximally concentrated urine. Samples of collecting duct fluid were obtained from the base and tip of the papilla by micropuncture through the intact ureter. Fluid osmolality rose sharply from base, 894+/-120 mosmol/kg H(2)O(-1) (mean+/-SE), to tip, 1,667+/-114 (P<0.001), a distance of only 2 mm, and was due exclusively to reabsorption of water. After excision of the ureter, which abolished intermittent flow, osmolality fell modestly at the base to 723+/-82 mosmol/kg H(2)O(-1) (P < 0.02), but strikingly at the tip to 1,012+/-103 (P < 0.001). The pelvic ureter was paralyzed by topical verapamil and dimethylsulfoxide, which abolished intermittent flow. Osmolality of urine at the tip was not changed (1,959+/-184 mosmol/kg H(2)O(-1) before, vs. 1,957+/-126 after paralysis). The ureter was severed just beyond the papillary tip, a maneuver which preserved intermittent flow but abolished urinary reflux over the papilla. Urinary osmolality fell from 1,876+/-134 mosmol/kg H(2)O(-1) to 1,284+/-115 (P < 0.005). These findings demonstrate that when the ureter is intact, over half of the increase in urinary osmolality above isotonicity occurs in the terminal one-fourth of the medullary collecting duct and is due exclusively to water reabsorption (no net solute addition). It is the continuity of the ureter, rather than intermittent flow due to ureteral peristalsis, which is essential for the formation of a maximally concentrated urine.
View details for Web of Science ID A1982NA38100019
View details for PubMedID 7054236
EFFECT OF FUROSEMIDE ON SODIUM AND POTASSIUM FLOW AT THE END OF THE JUXTAMEDULLARY DESCENDING-LIMB IN PSAMMOMYS-OBESUS
RENAL PHYSIOLOGY AND BIOCHEMISTRY
1982; 5 (3): 105-114
To examine the effect of reducing medullary interstitial solute concentration on sodium and potassium flow at the end of the juxtamedullary descending limb in Psammomys obesus, micropuncture was performed on the exposed left renal papilla. After a control period, furosemide was administered to reduce medullary interstitial solute concentration without altering the delivery of sodium, potassium and water from the proximal tubule. The fraction of filtered sodium remaining at the end-descending limb before (52 +/- 4.9%) and after furosemide (55 +/- 4.2%) was not significantly different, despite a fall in tubule-to-plasma osmolality from 4.32 to 2.00 (p less than 0.001). In contrast, the fraction of filtered potassium delivered to the end-descending limb fell from 92 +/- 9.0% to 61 +/- 8.0% (p less than 0.001). As expected, the fraction of filtered sodium and potassium remaining at the end of the accessible proximal tubule of the superficial nephron was not changed after the administration of furosemide. While these findings do not provide additional support for the thesis of transepithelial sodium addition to the juxtamedullary descending limb, they strongly suggest that transepithelial entry (secretion) of potassium normally occurs upstream to the juxtamedullary hairpin turn of Psammomys obesus.
View details for Web of Science ID A1982NN63100001
View details for PubMedID 7048466
EFFECTS OF ACUTE ACID-BASE DISTURBANCES ON K+ DELIVERY TO THE JUXTAMEDULLARY END-DESCENDING LIMB
AMERICAN JOURNAL OF PHYSIOLOGY
1982; 243 (2): F188-F196
Effects of acute-base disturbances on fractional delivery of potassium to the juxtamedullary end-descending limb were examined by micropuncture in the rat to test the hypothesis that potassium is reabsorbed from the collecting duct and is secreted in juxtamedullary pars recta or descending limb in the renal medulla. In metabolic acidosis, fractional potassium delivery was only slightly reduced compared with control values and was a function of potassium excretion, as the hypothesis predicts. Fractional potassium delivery was sharply reduced both in respiratory acidosis and metabolic alkalosis and was no longer a function of potassium excretion. Although seemingly inconsistent with the recycling hypothesis, the latter finding may be reconciled by the following observations. In respiratory acidosis, vasa recta blood flow nearly doubled, which would lead to vascular washout of interstitial potassium. In metabolic alkalosis, flow rate in the pars recta or descending limb was reduced by 28%, which would limit transepithelial potassium addition. The results indicate complex effects of acid-base disturbances on fractional potassium delivery to the end-descending limb, which can be unified by postulated changes in transepithelial potassium concentration differences across the juxtamedullary pars recta or descending limb. An unexpected observation emerged--fractional delivery of water to the end-descending limb declined as a function of plasma bicarbonate concentration when all groups were combined.
View details for Web of Science ID A1982PC51800061
View details for PubMedID 7114218
NEW PATHWAYS FOR POTASSIUM-TRANSPORT IN THE KIDNEY
AMERICAN JOURNAL OF PHYSIOLOGY
1982; 242 (4): F297-F312
This review focuses on the hypothesis that potassium is recycled in the medulla by secretion into the pars recta or descending limb of long-looped nephrons and reabsorption from the ascending limb and/or medullary collecting duct. Evidence supporting the recycling hypothesis is summarized and the process is analyzed quantitatively by an examination of the mass flow of potassium reaching different sites along superficial and juxtamedullary nephrons and collecting tubules. From differences in potassium mass flow between sites, we have estimated the amount of potassium that must be secreted or absorbed by individual segments of the renal tubule. These rates of secretion and absorption are compared with the potassium transport characteristics of the respective segments, as assessed by isolated tubule perfusion in vitro and micropuncture in vivo. It is apparent that potassium secretion can occur passively in the pars recta and descending limb of long-looped nephrons as a consequence of the elevated potassium concentration in the medullary interstitium. At present, no active potassium absorptive mechanism has been demonstrated in any segment of the ascending limb. Due to the very high ionic permeability of the thin ascending segment and the lumen-positive transepithelial voltage in the thick ascending segment, however, considerable passive absorption likely occurs, although net potassium secretion has also been demonstrated in the cortical thick ascending limb. The high potassium concentration in the inner medullary interstitium and the difference in mass flow of potassium between the end of superficial nephrons in the cortex and the collecting ducts in the papilla, at least under certain circumstances, are best accounted for by net potassium reabsorption in the medullary collecting duct.
View details for Web of Science ID A1982NL10200066
View details for PubMedID 7039362
POTASSIUM RECYCLING IN THE RENAL MEDULLA AND NEWER ASPECTS OF POTASSIUM-TRANSPORT
SEMINARS IN NEPHROLOGY
1982; 2 (4): 328-335
View details for Web of Science ID A1982PX71500006
GLOMERULAR AND TUBULAR FUNCTION IN NONOLIGURIC ACUTE-RENAL-FAILURE
AMERICAN JOURNAL OF MEDICINE
1982; 72 (4): 642-649
Glomerular and tubular function were evaluated in 30 non-oliguric patients with increasing azotemia following open heart surgery. Fractional clearances (theta) of test solutes relative to that of inulin were determined. In 16 patients, theta dextran (radius 22 to 30 A) exceeded unity, a finding attributed to inulin backleak through necrotic tubules. These patients were classified as having acute renal failure; 14 subsequently required dialysis. In the remaining patients (N = 14), theta dextran was normal. These patients were considered to have prerenal failure; all recovered spontaneously. clearance of inulin (Cin) was lower in acute renal failure than in prerenal failure (12 +/- 2 versus 18 +/- 2 ml/min/1.73 m2; p less than 0.025). The apparent difference in glomerular filtration rate when Cin is used as an index was abolished, however, when Cin in acute renal failure was corrected for tubule backleak of inulin. In acute renal failure, fractional clearance of p-aminohippurate (theta PAH) was 7.1 +/- 1.0, and fractional excretion of potassium (FEk) was 160 +/- 18 percent. These findings strongly suggest that secretory ability in both proximal and terminal tubule augments, respectively, is preserved in acute renal failure. Compared with prerenal failure, the urine-to-plasma inulin ratio was lower (U/Pin = 10 +/- 1 versus 25 +/- 4; p less than 0.005) and FENa was higher (FENa = 5.1 +/- 1.5 versus 0.5 +/- 1.0 percent; p less than 0.01) in acute renal failure.
View details for Web of Science ID A1982NL77600017
View details for PubMedID 6176124
- MEASURING SPECIFIC-GRAVITY OF URINE LANCET 1982; 2 (8312): 1396-1396
- COLLECTING DUCT FUNCTION AND SODIUM-BALANCE ANNUAL REVIEW OF MEDICINE 1982; 33: 241-254
MICROPUNCTURE STUDY OF THE SUPERFICIAL NEPHRON OF PEROGNATHUS-PENICILLATUS
AMERICAN JOURNAL OF PHYSIOLOGY
1981; 241 (6): F612-F617
A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.
View details for Web of Science ID A1981MX92000043
View details for PubMedID 7325232
POTASSIUM RECYCLING IN THE RENAL MEDULLA - EFFECTS OF ACUTE KCL ADMINISTRATION TO RATS FED A POTASSIUM-FREE DIET
1981; 20 (3): 348-352
According to the hypothesis of potassium recycling in the renal medulla, a portion of potassium in fluid in the medullary collecting duct is reabsorbed, trapped in the medullary interstitium by countercurrent exchange, and secreted in either the pars recta or descending limb of the juxtamedullary nephron. To examine the effects of an acute change in potassium balance on recycling, we performed a micropuncture study on the exposed papilla of 8 chloride. A second group of 6 rats was studied under identical conditions and infused with potassium chloride and amiloride. In the first group, the fraction of filtered potassium remaining at the end of the juxtamedullary descending limb increased with time to values over 100% concomitantly with the rise in urinary excretion of potassium. A strong association was found between those two variables (P less than 0.025). In the second group, in which the increase in urinary fractional excretion of potassium was prevented by amiloride, the rise in fractional of filtered potassium remaining at the end of the juxtamedullary nephron was abolished. These findings are interpreted as providing further support for the hypothesis of medullary recycling of potassium.
View details for Web of Science ID A1981MK65500005
View details for PubMedID 7300124
PHOSPHATE REABSORPTION IN JUXTAMEDULLARY NEPHRON TERMINAL SEGMENTS
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
1980; 387 (1): 27-31
Adult Munich Wistar rats undergoing mild salt diuresis (NaCl 20 g x l-1, 0.1 ml x min-1) were injected with tracer doses of 3H-Inulin and 32P-sodium phosphate in thin descending and ascending limbs of Henle's loop, collecting ducts accessible at the surface of the papilla and early distal superficial tubules. Kidneys were prepared for simultaneous papillar microinjection and urinary flow collection. Expressed in percent of the amounts injected, unidirectional phosphate reabsorption fluxes were 5 +/- 1% and 3 +/- 1% for injections into early distal superficial tubules and collecting ducts, respectively. By contrast, the flux was 21.7 +/- 3% for injections into either the descending or ascending thin limbs of juxtamedullary nephrons. We conclude from these results that in the rat, a significant amount of phosphate is reabsorbed by the juxtamedullary distal tubules and/or the subsequent arcades connecting the juxtamedullary distal tubules to the collecting ducts.
View details for Web of Science ID A1980KJ40400004
View details for PubMedID 7191102
TERMINAL PAPILLARY COLLECTING DUCT REABSORPTION OF WATER, SODIUM, AND POTASSIUM IN PSAMMOMYS-OBESUS
AMERICAN JOURNAL OF PHYSIOLOGY
1980; 239 (6): F539-F544
Micropuncture studies were performed to assess the contribution of the terminal collecting duct to reabsorption of water, sodium, and potassium in the desert rodent, Psammomys obesus. Tubule fluid was collected at base and tip of the exposed papilla before (period I) and after (period II) administration of furosemide. In period I, a significant rise occurred in tubule fluid-to-plasma (TF/P) ratios of inulin, osmolality, and sodium and potassium from base to tip; 2.3 +/- 0.8% of filtered water and 5.1 +/- 1.7% of filtered sodium were reabsorbed by the collecting duct. In period II water, sodium, and potassium delivery to the collecting duct was significantly increased. Although TF/P ratios for inulin, osmolality, and sodium and potassium were lower at base and tip in period II than corresponding values in period I, all ratios increased between base and tip. Approximately 3 times as much water (7.4 +/- 1.8%) and twice as much sodium (10.1 +/- 3.0%) were reabsorbed by the exposed collecting duct in period II. These results reveal a remarkable reabsorptive capacity and suggest that the terminal collecting duct plays an important role in regulation of water and sodium excretion in Psammomys obesus.
View details for Web of Science ID A1980KW24800055
View details for PubMedID 7004210
DIABETES-INSIPIDUS - A PHYSIOLOGIC APPROACH TO DIAGNOSIS
1980; 68 (6): 120-?
Diabetes insipidus can be delineated in the context of the normal physiology of water metabolism. This approach highlights the common pathway taken by the variety of diseases that can progress to an insufficiency of antidiuretic hormone (ADH) and to diabetes insipidus. A simple diagnostic approach uses homeostatic pathways to separate diabetes insipidus from the other polyuric states. New developments in the biochemical alteration of ADH have improved the ability to individualize hormonal replacement and promise better therapy in the near future.
View details for Web of Science ID A1980KT01600016
View details for PubMedID 7433311
EFFECT OF PROSTAGLANDIN INHIBITION ON ERYTHROCYTE VELOCITIES IN VASA RECTA OF WATER LOADED RATS
SLACK INC. 1980: A63–A63
View details for Web of Science ID A1980JB49200374
EFFECT OF PROSTAGLANDIN INHIBITION ON RBC VELOCITIES IN VASA RECTA OF THE RENAL MEDULLA
SLACK INC. 1980: A534–A534
View details for Web of Science ID A1980JN16002293
NEED FOR FACULTY MEMBERS IN RENAL RESEARCH IN CLINICAL DEPARTMENTS - REPORT OF THE SCIENTIFIC ADVISORY BOARD OF THE NATIONAL-KIDNEY-FOUNDATION
1980; 17 (1): 135-138
To provide an approximate estimate of the need for academic faculty in renal research, 1200 questionnaires were mailed to most departments in all medical schools in the United States. There were 627 completed questionnaires returned from 99 divisions of nephrology, 79 divisions or departments of urology, and 67 divisions of pediatric nephrology or departments of pediatrics in 120 medical schools. Analysis of the responses revealed that in these three departments there are 1057 faculty members engaged in teaching and research related to the kidney and urinary tract, and 131 current vacancies. The responses suggest that from 1979 to 1984 another 483 faculty members will be required to fill projected vacancies in the foregoing three clinical departments, making the total needed 614.
View details for Web of Science ID A1980JF55600015
View details for PubMedID 7374016
Questions and replies: role of the collecting tubule in fluid, sodium, and potassium balance.
The American journal of physiology
1979; 237 (4): F247-61
In terms of day-to-day regulation of fluid and electrolyte balance, the collecting tubule system appears to occupy a paramount position among segments of the renal tubule. Controversy has arisen concerning the quantitative contribution by the collecting tubule system to the regulation of individual solute excretion, which in part may be due to differences among the investigative techniques employed. In this Editorial Review, R. L. Jamison summarizes current views on the function of the collecting tubule system, particularly with regard to regulation of sodium and potassium excretion, and then poses seven questions pertaining to this topic. H. Sonnenberg, who has revived the microcatheterization technique, and J. H. Stein, whose group has employed the micropuncture method, respond to these questions. The key issues addressed are: 1) the principal factors that influence transtubular movement of sodium and potassium across the collecting tubule; 2) the limitations and potential artifacts of the microcatheterization and micropuncture techniques when used to examine the function of the collecting tubule; 3) apparent discrepancies among results obtained by micropuncture in vivo, microcatheterization in vivo, and microperfusion in vitro of the collecting tubule; and 4) major unresolved questions concerning the function of the collecting tubule.
View details for PubMedID 386805
URINARY CONCENTRATING MECHANISM IN THE DESERT RODENT PSAMMOMYS-OBESUS
AMERICAN JOURNAL OF PHYSIOLOGY
1979; 236 (5): F448-F453
The mechanism by which osmolality rises in fluid in the juxtamedullary descending limb was examined in Psammomys obesus by micropuncture of the left renal papilla. The concentration of Na, Cl, K, Mg, and phosphorus was determined by electron probe; Cl concentration by both probe and the microcoulometric technique of Ramsay et al. (J. Exp. Biol. 32: 822--829, 1955). The mean urine-to-plasma ultrafiltrate (U/P) osmolality was 5.5 +/- 0.46 (SE). In 43 samples obtained from the end-descending limb in 16 animals, mean values were: tubule fluid-to-plasma ultrafiltrate (TF/P) osmolality, 3.64 +/- 0.30; (TF/P)In, 6.96 +/- 0.52; (TF/P)Na, 3.53 +/- 0.27; (TF/P)Cl-e, 4.11 +/- 0.37 (-e is electron probe determination); and (TF/P)Cl-r, 4.25 +/- 0.37 (-r is determination by method of Ramsay). In terms of percentage of filtered ion remaining at the end-descending limb, Na was 54 +/- 3.7%, Cl-e was 61 +/- 3.6%, and Cl-r was 63 +/- 4.0%. The percentage of filtered chloride remaining averaged 80% or more in three animals, equalled or slightly exceeded 100% in six individual descending limb samples, and in all animals was a function of loop fluid osmolality (y = 8.61x + 31.9, r = 0.66, P less than 0.01). The results are most consistent with the thesis that both water extraction and transepithelial NaCl addition contribute to the rise in osmolality of fluid in the descending limb of the Psammomys.
View details for Web of Science ID A1979GV96700066
View details for PubMedID 443382
ROLE OF THE COLLECTING TUBULE IN FLUID, SODIUM, AND POTASSIUM-BALANCE - QUESTIONS AND REPLIES
AMERICAN JOURNAL OF PHYSIOLOGY
1979; 237 (4): F247-F261
View details for Web of Science ID A1979HR42500029
- ERYTHROCYTE VELOCITY IN VASA RECTA - EFFECT OF ANTI-DIURETIC HORMONE AND SALINE LOADING AMERICAN JOURNAL OF PHYSIOLOGY 1979; 237 (4): F326-F332
SUPPRESSION OF POTASSIUM-RECYCLING IN THE RENAL MEDULLA BY SHORT-TERM POTASSIUM DEPRIVATION
1979; 16 (6): 704-709
Recently we proposed that potassium, like urea, normally undergoes medullary recycling from collecting tubule to the pars recta or descending limb of the juxtamedullary nephron and suggested that the extent of recycling is a function of the concentration of potassium in collecting tubule fluid. To test this hypothesis further, we fed young rats a potassium-free diet for 3 days and then prepared them for micropuncture of the left renal papilla. Compared to findings in normally fed animals, potassium deprivation caused a significant fall in plasma potassium and urinary excretion of potassium. There was a striking decrease in the fraction of filtered potassium remaining at the end of the justamedullary descending limb for 94 +/- 11% to 38 +/- 3% (P less than 0.001). The latter value is not significantly different from the fraction of filtered sodium remaining (36 +/- 4%) and suggests that net addition of potassium to the pars recta or descending limb was completely abolished. A correlation was observed between the fraction of filtered potassium remaining at the end of the descending limb and either urinary potassium excretion (P less than 0.001) or urinary potassium concentration(P less than 0.001) in the contralateral unexposed kidney. These results lend further support to the hypothesis of medullary recycling of potassium.
View details for Web of Science ID A1979HY94000006
View details for PubMedID 548609
- DETERMINATION OF ERYTHROCYTE VELOCITIES IN THE MAMMALIAN INNER RENAL MEDULLA BY A VIDEO VELOCITY-TRACKING SYSTEM MICROVASCULAR RESEARCH 1979; 18 (3): 370-383
ACUTE RENAL-FAILURE FOLLOWING CARDIAC-SURGERY
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
1979; 77 (6): 880-888
In a prospective 6 month study of 204 patients requiring cardiac operations, five (2.5 percent) developed acute renal failure (ARF) and five (2.5 percent) had documented renal dysfunction (RD). Preoperative left ventricular dysfunction and prolonged cardiopulmonary bypass (CPB) were important predictors of subsequent RD/ARF; CPB pressure per se was not. Physiological and clinical studies in 51 selected patients studied over an 18 month period documented the effectiveness of low flow, low pressure CPB in preserving postoperative renal function. Twenty-two patients with nonazotemic postoperative courses demonstrated moderate depression of cardiac function while the glomerular filtration rate (GFR) was normal (98 +/- 30 ml./min/1.73 M.2) within 24 hours of operation. Seventeen high risk patients developed AFF (65 percent mortality rate) and 12 experienced severe RD without ARF (17 percent mortality). ARF (65 percent mortality rate) and 12 experienced severe RD without ARF (17 percent mortality). Eleven patients with ARF and 11 with RD were studied in the early postoperative period; at this time, all 22 patients demonstrated RD with equivalent severe depression of cardiac and renal function. Superposition of further hemodynamic or toxic insults upon ischemic kidneys was usually necessary for ARF to occur.
View details for Web of Science ID A1979GZ22800015
View details for PubMedID 439924
RECENT FORMULATIONS OF THE URINARY CONCENTRATING MECHANISM - STATUS-REPORT
1979; 16 (5): 537-545
The status of the purely passive mode of solute concentration as of 1979 appears to be similar to that of the original countercurrent hypothesis 10 years ago. The passive mode concept has advanced our understanding of the concentrating process by qualitatively incorporating the permeability characteristics of tubule segments and the lack of an active transport process in the thin loop of Henle into a mechanism which has attractive economy and explanatory value. But in the final analysis some assumptions are not borne out by experimental findings (for example, the high urea concentration of fluid in the rat and hamster end-descending limb; the likelihood of net transepithelial addition of sodium chloride to the Psammomys descending limb; the removal of sodium chloride from the hamster ascending limb against an apparent electrochemical gradient under certain circumstances; and the osmotic lag between vasa recta blood and interstitium in the rat). Furthermore, when the known permeability and transport characteristics of the renal tubule are incorporated into a mathematic model of the passive operating mode, numerical simulations fail to establish a progressively hyperosmotic inner medulla. This does not rule out the applicability of the more general model (Eq. 1), particularly if evidence for some form of active transport in the inner medulla, heretofore lacking, is forthcoming.
View details for Web of Science ID A1979HV72700001
EFFECT OF CHRONIC POTASSIUM LOADING ON POTASSIUM SECRETION BY PARS RECTA OR DESCENDING LIMB OF JUXTAMEDULLARY NEPHRON IN RAT
JOURNAL OF CLINICAL INVESTIGATION
1978; 62 (5): 1093-1103
Recently we demonstrated potassium secretion by the pars recta or by the descending limb of the juxtamedullary nephron. The purpose of this present investigation is to study the effect of a chronic high-potassium intake on this phenomenon. Fractional reabsorption of water and sodium by the juxtamedullary proximal nephron was decreased when compared to that in normal hydropenic rats. There was a striking increase in the fraction of filtered potassium at the end of the juxtamedullary descending limb from 94+/11% to 180+/18%, which was principally a result of enhanced potassium secretion. When the concentration of potassium in the collecting tubule fluid of potassium-loaded rats was reduced after the administration of amiloride, a sharp fall was observed in the amount of potassium which reached the end of the descending limb (64+/8%). A direct correlation was observed between the fraction of filtered potassium at the descending limb and the potassium concentration in the final urine (P less than 0.001). The findings suggest that potassium, like urea, normally undergoes medullary recycling, which is enhanced by chronic potassium loading.
View details for Web of Science ID A1978FU15600025
View details for PubMedID 711855
EFFECT OF VOLUME EXPANSION (VE) ON RENAL INNER MEDULLARY BLOOD-FLOW
SLACK INC. 1978: A464–A464
View details for Web of Science ID A1978EU89401515
- TRANS-EPITHELIAL GRADIENT AND FRACTIONAL DELIVERY OF CHLORIDE IN THIN LOOP OF HENLE AMERICAN JOURNAL OF PHYSIOLOGY 1978; 235 (3): F192-F198
- EFFECT OF ANTIDIURETIC HORMONE-INDUCED ANTIDIURESIS ON WATER REABSORPTION BY SUPERFICIAL LOOP OF HENLE IN BRATTLEBORO RATS JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1977; 90 (6): 1004-1011
EVIDENCE FOR A CONCENTRATION GRADIENT FAVORING OUTWARD MOVEMENT OF SODIUM FROM THIN LOOP OF HENLE
JOURNAL OF CLINICAL INVESTIGATION
1977; 59 (2): 234-240
Recent models of the urinary concentrating mechanism have postulated that urea in the medullary interstitium creates a transtubular concentration gradient for sodium between fluid at the end of the descending limb of Henle's loop and the medullary interstitium, favoring the passive outward movement of sodium from Henle's thin ascending limb. These experiments were designed to determine whether such a gradient normally exists. Young nondiuretic Munich-Wistar rats were prepared for micropuncture of the exposed left renal papilla. Samples of loop of Henle fluid and vasa recta plasma (assumed to reflect the composition of interstitial fluid) were obtained from adjacent sites. Loop fluid values in 21 comparisons from 18 rats (mean +/- SE) were: sodium 344 +/- 12 meq/liter; potassium, 26 +/- 2 meq/liter; osmolality, 938 +/- 37 mosmol/kg H23. Vasa recta plasma values (in corresponding units of measurement) were: sodium, 284 +/- 11; potassium, 34 +/- 2; osmolality, 935 +/- 34. Mean values of paired differences (loop fluid minus vasa recta plasma) were: delta sodium, 60 +/- 11.1 (P less than 0.001); delta potassium, -8.0 +/- 2.1 (P less than 0.001); delta osmolality, 4 +/- 16 (NS). Corrected for plasma water, the loop fluid minus vasa recta differences (in milliequivalents per kilogram H2O) were: delta sodium, 40 +/- 11.4 (P less than 0.005); delta potassium, -9.7 +/- 1.9 (P less than 0.001). We interpret these findings to indicate that in the papilla of nondiuretic rats, a significant difference in sodium concentration exists across the thin loop of Henle favoring outward movement of sodium, which confirms a key requirement of the passive models. A concentration difference for potassium in the reverse direction was also observed.
View details for Web of Science ID A1977CU60400006
View details for PubMedID 833272
- SOURCE OF INULIN IN SAMPLES OF VASA RECTA BLOOD ANNALS OF BIOMEDICAL ENGINEERING 1977; 5 (1): 85-94
WATER EXTRACTION FROM INNER MEDULLARY COLLECTING TUBULE SYSTEM - ROLE FOR UREA
1976; 10 (2): 139-146
Recent examinations of the inner medullary collecting tubule membrane in vitro have demonstrated that its reflection coefficient to urea (sigma urea) is significantly less than unity and less than sigma NaClhe presence of antidiuretic hormone. Fluid entering the inner medullary collecting tubule has a higher urea concentration and lower NaCl concentration than does the medullary interstitium, although total osmolarity is nearly equal on either side of the membrane. The transtubular difference in solute composition, together with the difference between sigma urea and sigma NaCl, should result in a driving force for extraction of water from the tubule. This hypothesis was examined in a differential analysis of water and solute fluxes across the collecting tubule epitheliu. The results indicate that this driving force contributes significantly to water extraction from the inner medullary collecting tubule.
View details for Web of Science ID A1976CD47300002
View details for PubMedID 966451
NON-INVASIVE DETERMINATION OF ERYTHROCYTE VELOCITIES IN MAMMALIAN INNER RENAL MEDULLA
NATURE PUBLISHING GROUP. 1976: 584–84
View details for Web of Science ID A1976CS83900405
EXAMINATION OF TRANSCAPILLARY WATER FLUX IN RENAL INNER MEDULLA
AMERICAN JOURNAL OF PHYSIOLOGY
1976; 231 (2): 313-318
We recently demonstrated that net fluid uptake occurs in the capillary system of the inner medulla. To define the site of fluid uptake, the concentration of protein was determined in plasma from descending vasa recta at the base and tip of the exposed papilla in Munich-Wister rats. The vasa recta plasma-to-arterial plasma protein concentration ratio (VR/P) was 1.43 +/- 0.09 at the base and 1.66 +/- 0.09 at the tip. These results, which indicate fluid loss from the descending vasa recta, are difficult to explain on the basic of hydraulic and oncotic forces alone. The osmolality of the contents of descending vasa recta increased between base and tip (delta = 72 +/- 30 mosmol/kg H2O). If the increase in osmolality of plasma in descending vasa recta lags behind that of the adjacent medullary interstitium, a transcapillary osmotic driving force exists favoring water loss from descending vessels. It is concluded that fluid uptake by the inner medullary circulation occurs beyond descending vasa recta in interconnecting capillaries or ascending vasa recta. In our view the most likely interpretation of these results is that fluid movement across vasa recta in the inner medulla is influenced by three forces: those owing to transcapillary differences in osmotic, oncotic, and hydraulic pressures.
View details for Web of Science ID A1976CC62600005
View details for PubMedID 961881
POTASSIUM SECRETION BY DESCENDING LIMB OR PARS RECTA OF JUXTAMEDULLARY NEPHRON INVIVO
1976; 9 (4): 323-332
Potassium reabsorption by the juxtamedullary nephron up to the hairpin turn was studied by the micropuncture technique in the exposed renal papilla of rats. In 18 nondiuretic rats, the fraction of filtered potassium remaining at the end of the desdending limb averaged 113 +/- 9%, indicating either that potassium is not reabsorbed by the juxtamedullary proximal tubule and descending limb or that potassium is reabsorbed and secreted in those segments. Furosemide, a drug which inhibits NaCl reabsorption in the ascending limb downstream from the descending limb, significantly decreased the potassium remaining at the end of the descending limb from 106 +/- 12 to 72 +/-11% in seven rats. Benzolamide, a drug which inhibits reabsorption of NaHCO3 and water in the proximal tubule upstream from the descending limb significantly increased the potassium remaining from 103 +/- 13 to 177 +/- 32% in eight rats. These findings support the hypothesis that in the rat, potassium is normally reabsorbed by the proximal convoluted tubule and secreted in the pars recta or descending limb of the juxtamedullary nephron.
View details for Web of Science ID A1976BS97900002
View details for PubMedID 940273
SOURCE OF INULIN IN PLASMA FROM VASA RECTA CAPILLARIES OF RENAL MEDULLA INVIVO
SLACK INC. 1976: A162–A162
View details for Web of Science ID A1976BT40400494
- URINARY CONCENTRATING MECHANISM NEW ENGLAND JOURNAL OF MEDICINE 1976; 295 (19): 1059-1067
HYDRAULIC AND ONCOTIC PRESSURE MEASUREMENTS IN INNER MEDULLA OF MAMMALIAN KIDNEY
AMERICAN JOURNAL OF PHYSIOLOGY
1975; 228 (6): 1921-1926
The vasa recta are thought to play an important role in the transfer of water andsolutes within the renal medulla. Hydraulic pressures were measured in vasa recta onthe surface of the exposed papilla in young Munich Wistar rats, and blood was collected from these microvessels for determination of total protein concentration and calculation of colloid oncotic pressure. In descending vasa recta at the base of the exposed papilla, mean hydraulic pressure was 9.2 plus or minus 0.4 (SE) mmHg and plasma protein concentration averaged 7.1 plus or minus 0.4 g/100 ml. Corresponding valuesin ascending vasa recta at the same level were 7.8 plus or minus 0.4 mmHg and 5.6 plusor minus 0.3 g/100 ml. respectively. The protein concentrations correspond to calculated oncotic pressures of 26 and 18 mmHg in descending and ascending vasa recta, respectively. We interpret these findings as evidence for net water uptake by the vasa recta in the renal inner medulla for which the driving forces are the transcapillary hydraulic and oncotic pressure differences.
View details for Web of Science ID A1975AJ22300047
View details for PubMedID 1155623
EFFECT OF UREA INFUSION ON URINARY CONCENTRATING MECHANISM IN PROTEIN-DEPLETED RATS
JOURNAL OF CLINICAL INVESTIGATION
1975; 55 (2): 399-409
To explore the role of urea in the urinary concentrating mechanism, the contents of vasa recta, Henle's descending limbs and collecting ducts were sampled by micropuncture of the renal papilla before and after infusion of urea in 10 protein-depleted rats. Eight protein-depleted rats not given urea were similarly studied as a control group. After urea administration, osmolality and the concentrations of urea and nonurea solute of urine from both exposed and contralateral kideny increased significantly. The osmolality and urea concentration of fluid from the end of Henle's descending limb and vasa recta plasma and the tubule fluid-to-plasma inulin ratio in the end-descending limb all increased significantly after urea infusion. We interpret these observations to indicate that urea enhances urinary concentration by increasing the abstraction of water from the juxtamedullary nephron (presumably the descending limb), in agreement with the prediction of recent passive models of the urinary concentrating mechanism. However, the concentration of urea in fluid from the descending limb after urea infusion was high (261 plus or minus 31 mM) and the difference in solium concentration between descending limb fluid and vasa recta was small and statistically insignificant.
View details for Web of Science ID A1975V453000022
View details for PubMedID 1127107
- CALCIUM REABSORPTION IN THIN LOOP OF HENLE AMERICAN JOURNAL OF PHYSIOLOGY 1974; 227 (3): 745-751
RECENT ADVANCES IN PHYSIOLOGY OF HENLES LOOP AND COLLECTING TUBULE SYSTEM
1974; 34: I91-I100
View details for Web of Science ID A1974T740100011
PRESSURE MEASUREMENTS IN RAT RENAL MEDULLA
FEDERATION AMER SOC EXP BIOL. 1974: 387–87
View details for Web of Science ID A1974S334301006
- ROLE OF CELLULAR SWELLING IN PATHOGENESIS OF ORGAN ISCHEMIA WESTERN JOURNAL OF MEDICINE 1974; 120 (3): 205-218
- INVIVO STUDY OF CONCENTRATING PROCESS IN DESCENDING LIMB OF HENLES LOOP KIDNEY INTERNATIONAL 1974; 5 (5): 337-347
- INTRARENAL HETEROGENEITY - CASE FOR 2 FUNCTIONALLY DISSIMILAR POPULATIONS OF NEPHRONS IN MAMMALIAN KIDNEY AMERICAN JOURNAL OF MEDICINE 1973; 54 (3): 281-289
- MICROPUNCTURE STUDY OF HENLES THIN LOOP IN BRATTLEBORO RATS AMERICAN JOURNAL OF PHYSIOLOGY 1973; 224 (1): 180-185
- EVIDENCE FOR FUNCTIONAL INTRARENAL HETEROGENEITY OBTAINED BY MICROPUNCTURE TECHNIQUE YALE JOURNAL OF BIOLOGY AND MEDICINE 1972; 45 (3-4): 254-?
- PHOTOMETRIC DETERMINATION OF PICOMOLE QUANTITIES OF CALCIUM ANALYTICAL CHEMISTRY 1972; 44 (8): 1523-?
- EVIDENCE FOR URINARY DILUTION BY COLLECTING TUBULE AMERICAN JOURNAL OF PHYSIOLOGY 1972; 223 (4): 898-?
- NO REFLOW PHENOMENON IN RENAL ISCHEMIA LABORATORY INVESTIGATION 1971; 25 (6): 635-?
MICROPUNCTURE STUDY OF COLLECTING TUBULE FUNCTION IN RATS WITH HEREDITARY DIABETES INSIPIDUS
JOURNAL OF CLINICAL INVESTIGATION
1971; 50 (11): 2444-?
The reabsorption of water and solute by the papillary collecting duct was studied during water diuresis and vasopressin-induced antidiuresis in young rats with hereditary hypothalamic diabetes insipidus. The tip of the left renal papilla was exposed and fluid was obtained by micropuncture from loops of Henle and from collecting ducts at the papillary tip, and at an average of 1 mm proximal to the tip. In water diuresis the ratio of tubule fluid to plasma (TF/P) osmolality (osm) of loop fluid was 1.73 +/-0.058 (SE); of fluid from the proximal collecting duct, 0.63 +/-0.027; and from the tip, 0.55 +/-0.024; indicating a substantial osmotic pressure difference across the collecting duct epithelium. The fraction of filtered water reabsorbed (x 100) by the terminal collecting duct was 1.58% +/-0.32. In antidiuresis the TF/P osm of loop fluid was 2.65 +/-0.109; of fluid from the proximal collecting duct, 2.20 +/-0.093; and from the tip, 2.71 +/-0.111; indicating a marked decrease in the driving force for water reabsorption. The fraction of filtered water reabsorbed (x 100) by the terminal collecting duct was reduced to 0.58% +/-0.08, while the delivery of solute to the same segment was unchanged from that in water diuresis. The glomerular filtration rate (GFR) of the right kidney declined from 327 +/-24.4 mul/min in water diuresis to 274 +/-24.4 mul/min in antidiuresis (P < 0.005); similar results were obtained in a study comparing right and left GFRs in five additional rats. Thus, fractional reabsorption (and very likely the absolute volume) of water reabsorbed by the terminal collecting duct was less in antidiuresis than in water diuresis (mean difference, 1.01% +/-0.29, P < 0.005).
View details for Web of Science ID A1971K752700024
View details for PubMedID 5096527
- EFFECT OF SALINE INFUSION ON SUPERFICIAL AND JUXTAMEDULLARY NEPHRONS IN RAT AMERICAN JOURNAL OF PHYSIOLOGY 1971; 221 (3): 690-?
- RENAL FUNCTION IN CHINCHILLA AMERICAN JOURNAL OF PHYSIOLOGY 1970; 219 (6): 1706-?
- MICROPUNCTURE STUDY OF SUPERFICIAL AND JUXTAMEDULLARY NEPHRONS IN RAT AMERICAN JOURNAL OF PHYSIOLOGY 1970; 218 (1): 46-?
- MICROPUNCTURE STUDY OF SEGMENTS OF THIN LOOP OF HENLE IN RAT AMERICAN JOURNAL OF PHYSIOLOGY 1968; 215 (1): 236-?
- AN AIR-DRIVEN MICROPIPETTE SHARPENER JOURNAL OF APPLIED PHYSIOLOGY 1967; 22 (1): 191-?
- COUNTERCURRENT MULTIPLICATION BY THIN LOOPS OF HENLE AMERICAN JOURNAL OF PHYSIOLOGY 1967; 212 (2): 357-?
- A METHOD FOR EXPOSING RAT RENAL MEDULLA IN VIVO - MICROPUNCTURE OF COLLECTING DUCT AMERICAN JOURNAL OF PHYSIOLOGY 1965; 209 (3): 663-?
Closed-chest cardiac massage in the treatment of ventricular fibrillation complicating acute myocardial infarction.
New England journal of medicine
1962; 267: 679-681
View details for PubMedID 14476523
CLOSED-CHEST CARDIAC MASSAGE IN TREATMENT OF VENTRICULAR FIBRILLATION COMPLICATING ACUTE MYOCARDIAL INFARCTION - REPORT OF 3 CASES WITH SURVIVAL
NEW ENGLAND JOURNAL OF MEDICINE
1962; 267 (14): 679-?
View details for Web of Science ID A19628540B00008
- ACTION OF A MERCURIAL DIURETIC ON ACTIVE SODIUM TRANSPORT, ELECTRICAL POTENTIAL AND PERMEABILITY TO CHLORIDE OF ISOLATED TOAD BLADDER JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1961; 133 (1): 1-?