bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin B12 uptake in dog kidney: its use as an extracellular reference marker
Authors: Silverman M.
Published: December 2017

The renal handling of [3H]cyanocobalamin has been investigated in dogs in vivo using the pulse injection multiple-indicator dilution technique. Simultaneous renal vein and urine outflow curves were obtained for [3H]cyanocobalamin relative to T-1824-albumin (plasma reference) and creatinine (extracellular reference). The renal vein recovery of [3H]cyanocobalamin relative to creatinine was significantly less than unity and increased with increasing intraarterial dose. This indicates a saturable postglomerular uptake mechanism. The urine recovery of [3H]cyanocobalamin relative to simultaneously filtered creatinine is also less than unity and increases with increasing intra-arterial doses. This indicates a saturable interaction at the luminal surface of the nephron. Saturation interaction at the luminal surface of the nephron. Saturation of postglomerular and luminal interactions can also be achieved by systemic preloading with unlabeled vitamin B12. After saturation the renal vein and urine recoveries for [3H]cyanocobalamin and creatinine become equal. However, significant differences can be observed between their renal vein mean transit times, depending on experimental conditions. During hydropenia [3H]cyanocobalamin behaves as a true extracellular marker and emerges in renal vein and urine outflows, superimposing on creatinine. During mannitol diuresis vitamin B12 still behaves as a glomerular marker, but its renal vein mean transit time is now significantly less than that of creatinine and its calculated postglomerular volume of distribution is reduced by approximately 15% of the available interstitial space.
Urinary concentrating ability during dehydration in the absence of vasopressin
Authors: Gellai M. , Edwards B. R. , Valtin H.
Published: December 2017

Despite the apparent absence of vasopressin (ADH), Brattleboro homozygotes [diabetes insipidus (DI) rats] can concentrate their urine when deprived of drinking water. Since other investigators have shown that reducing glomerular filtration rate (GFR) improves the concentrating ability of water-loaded dogs, the present studies were undertaken to quantify the magnitude and time course of changes in GFR during dehydration. Clearance experiments were performed in 10 conscious DI rats before and following 3, 6, 9, 12, 15, and 24 h of dehydration. Urine osmolality increased from 155.0 +/- 12.6 (SE) to 696.7 +/- 8.4 mosmol/kg H2O after 24 h. GFR averaged 984.3 +/- 79.6 microliters . min-1 . 100 g body wt-1 in the control phase, fell to about 80% of this value over the first 12 h of dehydration, and then declined to 27% at 24 h. The rats lost 20% of their body weight over the 24 h. The osmolality of the papillary tip averaged 896 +/- 44 mosmol/kg H2O at 24 h compared to a control value of 493 +/- 28. The lack of osmotic equilibration between urine and papillary interstitium suggests that dehydration did not appreciably increase the water permeability of the distal nephron. These experiments clearly show a progressive decline in GFR as urine becomes concentrated during dehydration in the absence of ADH; these events may or may not be causally related.
Hormonal regulation of active chloride transport in the dogfish rectal gland
Authors: Stoff J. S. , Rosa R. , Hallac R. , Silva P. , Epstein F. H.
Published: December 2017

Active transport of chloride is modulated by cyclic AMP in the rectal gland of Squalus acanthias. Vasoactive intestinal peptide (VIP) specifically activates the production of cyclic AMP by the gland and stimulates the secretion of chloride. Somatostatin inhibits VIP-induced secretion but has no effect alone. Both these peptides are present in the dogfish shark and may play an important role in electrolyte homeostasis.
Urate transport in the nephron
Authors: Weiner I. M.
Published: December 2017

This paper summarizes the literature on the sties of urate transport, secretory and reabosrptive, in the nephron. In the animals studied thus far the bulk of urate transport occurs in the proximal tubules. Two patterns of transport have been uncovered. In one, urate is secreted and reabsorbed throughout the convoluted tubule (perhaps the pars recta as well). The direction of net transport depends on the kind of animal studied and in some instances on the experimental conditions. In the second pattern there is a strong secretory process in the pars recta, and net secretion of urate, when it occurs, is attributable to that segment. In some but not all animals it is clear that urate secretion in the proximal tubules occurs by a mechanism separate from that which secretes p-aminohippurate (PAH). One important unresolved question is: How general is the occurrence of separate secretory mechanisms for PAH and urate? Another unresolved question is: What are the magnitudes of the unidirectional fluxes of urate in the segments in which bidirectional transport occurs?
Regional renin release by the cat kidney in vitro and in vivo
Authors: Jones S. M. , Torretti J. , Williams J. S. , Weinberger S. F.
Published: December 2017

Differences in the rate of renin release by superficial and deep areas of the cat kidney cortex were studied in vitro and in vivo. Renin release in vitro by outer cortical slices was significantly higher than by their inner counterparts: 19.6 +/- 2.3 vs. 12.8 +/- 1.95 ng angiotensin I-h-1-mg fresh tissue-1-h of incubation-1. In vivo blood was sampled from subcapsular (outer cortical) and deep (inner cortical and medullary) renal venous circulation from anesthetized cats. Renal venous minus arterial plasma renin concentration was respectively, 4.3 +/- 1.12 and 1.9 +/- 1.04 ng angiotensin I-ml-1-h-1 (P less than 0.01). By assuming that in these experiments renal blood flow distribution was approximately equal to each of the two areas of venous drainage, as reported in the isolated perfused cat kidney, we infer from the regional differences in arteriovenous concentration that the rate of renin release of the outer cortex is higher than that of the innder cortex in the cat kidney in vivo. Tissue content of renin was found to decrease toward the deep cortex. The results support the concept that the rate of regional renin release correlates with tissue renin content, at least under the conditions of the present experiments.
Acute and chronic effects of vasopressin on blood pressure, electrolytes, and fluid volumes
Authors: Smith M. J. , Cowley M. J. , Guyton A. C. , Manning R. D.
Published: December 2017

Physiological levels of arginine vasopressin (AVP) were continuously infused 24 h/day into six dogs for periods ranging from 7 to 34 days. The acute and chronic responses of the mean arterial pressure (MAP), body fluid volumes, renal function indices, plasma electrolyte concentrations, plasma renin activity, and urinary electrolyte and water excretion rates were measured. MAP was unaffected acutely but rose significantly to a peak on day 9 before declining toward control. MAP was significantly and positively correlated with the plasma volume, but had a diphasic correlation with the plasma sodium concentration and the change in total body sodium. The plasma sodium concentration reached a relatively stable plateau that was maintained in spite of large changes in total body water. We conclude that AVP produces only a transient hypervolemic hypertension; that AVP is a natriuretic agent, either directly or indirectly, both acutely and chronically; and that chronically it is a more potent controller of the plasma sodium concentration than of the total body water except in extreme cases.
Effect of fasting on tubular phosphorus reabsorption
Authors: Beck N. , Webster S. K. , Reineck H. J.
Published: December 2017

In the thyroparathyroidectomized (TPTX) rat, fasting increased urinary phosphorus excretion by decreasing the tubular reabsorption of P1 (TRP) and resulted in hypophosphatemia. The administration of either sucrose or NaHCO3 prevented the metabolic acidosis associated with fasting and decreased the phosphaturia, indicating that the phosphaturia in fasting is in part due to metabolic acidosis. In rats on partial reduction of P1 intake selectively, the phosphaturic response to parathyroid hormone (PTH) was completely suppressed. On the other hand, the fasting rat partially retained the phosphaturic response to PTH, although dietary P1 intake was totally absent. These findings suggest that the renal P1 wasting in fasting may take place by dual mechanisms: a) the PTH-independent decrease in TRP, and b) an inability to totally suppress the response to PTH. Cyclic AMP generation in response to PTH, determined both in vivo and in vitro, was not measurably altered in fasting. However, the phosphaturic response to cyclic AMP was decreased in fasting, suggesting that the mechanism of partial resistance to PTH is probably not at but after cyclic AMP generation.
Slowly dialyzable stimulators of renal protein synthesis in urine
Authors: Harris R. H. , Best C. F.
Published: December 2017

Previously, we demonstrated that continuous intravenous reinfusion of half the urine output (1/2UR) in rats for 1 wk led to increased renal mass. This suggested that reduced renal excretory function, or the retention of urinary factors, was capable of stimulating renal growth. The present study was designed to examine renal protein synthesis during the early phase of this growth and to better define the nature of the stimuli. Compared with matched sham-manipulated control rats, rats subjected to 24 h of 1/2UR displayed significant increases in both the incorporation of tritiated leucine into protein and in the cellular uptake of leucine by renal cortical tissue in vitro. In addition, total protein content of the kidneys, but not of the liver, was significantly increased after 24 h of 1/2UR. Dialysis of urine prior to its reinfusion did not diminish, but rather augmented, the incorporation of leucine into renal protein. These results suggest that renal protein synthesis can be stimulated by the retention of factors in the urine that are poorly dialyzable.
Stimulation of rabbit renal PGE2 biosynthesis by dietary sodium restriction
Authors: Stahl R. A. , Attallah A. A. , Bloch D. L. , Lee J. B.
Published: December 2017

Immunoreactive prostaglandin E2 (PGE2) was measured in slices of renal papilla (P), outer medulla (OM), and cortex (C) before and after 30 min of incubation (biosynthesis) in Krebs-Ringer HCO3- buffer in rabbits on low (LS), normal (NS), and high (HS) sodium diets. The 24-h urine PGE2 was also measured daily for 10 days prior to incubation. Daily urine PGE2 was significantly higher (911 +/- 54 ng) in LS, decreasing to 605 +/- 33 at NS, and 558 +/- 48 ng at HS, Initial slice PGE2 was highest in P at LS (35.5 +/- 5.1 MICROGRAMS/G), 5.1 microgram/g), decreasing to 16.9 +/- 1.3 at NS and 18.0 +/- 2.6 micrograms/g at HS. Similar patterns were observed in OM and C, which were quantitatively much lower. PGE2 biosynthesis was highest at LS (P, 139 +/- 21; OM, 58.8 +/- 5.1; C, 0.20 +/- 0.05 micrograms.G-1.30 Min-1) and lowest at HS (P, 58.9 +/- 7.4; OM, 11.8 +/- 3.1; C, 0.07 +/- 0.01 micrograms.g-1.30 min-1). Although PGE2 concentration was higher in P than in OM, the percent increase in OM PGE2 biosynthesis on LS was 3--4 times greater than in P. Since OM is 28% and P is 2% of total renal mass, these results indicate that LS markedly stimulates PGE2 biosynthesis primarily in OM and to a lesser extent in P and C, findings suggesting an important role for OM PGE2 in the renal adaptation to sodium deprivation.
Acute reversal by saralasin of multiple intrarenal effects of angiotensin II
Authors: Steiner R. W. , Blantz R. C.
Published: December 2017

Glomerular hemodynamics were measured by micropuncture technique in the plasma volume-expanded Munich-Wistar rat in 1) a control group, 2) during a pressor infusion of angiotensin II (AII), and 3) during simultaneous infusions of AII and saralasin, which returned arterial pressure to normal. Respective values obtained in the three groups studied were: nephron filtration rate: 60 +/- 2 vs. 40 +/- 2 vs. 42 +/- 2 nl.min-1.g kidney wt-1; nepphron plasma flow: 263 +/- 13 vs. 106 +/- 5 vs. 165 +/- 13 nl. min-1.g kidney wt-1; LpA, the glomerular permeability coefficient: 0.090 +/- 0.009 vs. 0.033 +/- 0.005 vs. 0.103 +/- 0.020 nl.s-1.g kidney wt-1. mmHg-1; afferent arteriolar resistance: 10.2 +/- 0.7 vs. 25.1 +/- 1.3 vs. 19.7 +/- 3.3 10(9) dyn.s.cm-5; efferent arteriolar resistance: 7.8 +/- 0.5 vs. 22.0 +/- 0.9 vs. 10.8 +/- 1.7 10(9) dyn.s.cm-5. Saralasin acutely reversed the effect of AII on both efferent resistance and LpA, suggesting that AII does not decrease LpA by inducing a fixed anatomic change. For unclear reasons, saralasin did not reverse the increase in afferent resistance associated with infusion of AII. Saralasin infusion in high AII states may acutely affect glomerular hemodynamics by decreasing efferent resistance and increasing the glomerular permeability coefficient.
Bradykinin-induced renal hemodynamic alterations: renin and prostaglandin relationships
Authors: Flamenbaum W. , Gagnon J. , Ramwell P.
Published: December 2017

The present studies examined the role of the renin-angiotensin system as a modifier of the renal vasomotor response to bradykinin. Renal arterial bradykinin infusion (80 ng.kg-1.min-1) initially resulted in increased renal blood flow (RBF). The secretory rates of renin and prostaglandins increased after 60 min. With continued bradykinin administration (120 min) RBF and prostaglandin secretory rates returned toward control values, although renin secretory rate remained elevated (P less than 0.02). After prostaglandin synthetase inhibition, RBF decreased and bradykinin administration returned RBF to control values. Prostaglandin secretory rates decreased after meclofenamate (P less than 0.005). Continued bradykinin infusion resulted in a return of the renin secretory rate to control values. The administration of bradykinin after competitive inhibition of angiotensin II resulted in a sustained increase in renal blood flow. These results suggest that the initial bradykinin-induced renal hyperemia is only partially dependent on enhanced prostaglandin release, the increase in renin secretion by bradykinin infusion after prostaglandin synthetase inhibition is consistent with a bradykinin and renin interaction, and the lack of a sustained hyperemia after bradykinin is related to increased renin-angiotensin system activity.
Indirect evidence for enhancement of Na-K-ATPase activity with stimulation of rectal gland secretion
Authors: Silva P. , Stoff J. , Epstein F. H.
Published: December 2017

The relation between active chloride secretion and Na-K-ATPase activity was studied in the isolated perfused rectal gland of Squalus acanthias stimulated by cAMP and theophylline. Ouabain inhibited both secretion and oxygen uptake in stimulated glands. Stimulation of chloride secretion by cAMP and theophylline resulted in a six- to sevenfold rise in ouabain-inhibitable oxygen consumption. Intracellular sodium concentration decreased while intracellular potassium rose. These findings suggest activation of Na-K-ATPase. On the other hand, the activity of Na-K-ATPase in whole homogenates of rectal gland tissue was not increased after cAMP stimulation of the perfused gland, nor was ouabain binding increased. Calculated intracellular chloride concentration fell after secretion was stimulated in a way consistent with an action of cAMP to increase luminal permeability to chloride.
Renal concentrating defect in the hypokalemic rat is prostaglandin independent
Authors: Berl T. , Aisenbrey G. A. , Linas S. L.
Published: December 2017

The renal concentrating defect in the hypokalemic rat is prostaglandin independent. The present study was undertaken to test whether the renal concentrating defect in potassium-depleted rats is at least in part mediated by prostaglandins. Rats on a K-deficient (n = 12) and K-supplemented (n = 12) diet underwent a urinary concentrating test before and after prostaglandin inhibition with indomethacin. The drug did not alter maximal urinary osmolality in normokalemic rats. Likewise, the abnormal maximal urinary osmolality of K-depleted rats was not improved by prostaglandin inhibition (1,533 +/- 124 before and 1,475 +/- 88 mosmol/kg H2O after indomethacin). Control animals receiving a blank diluent instead of indomethacin showed no change in maximal concentrating ability between equally timed dehydration tests. Indomethacin caused no significant alterations in blood urea nitrogen or creatinine. Direct measurements of renal medullary prostaglandings revealed no difference between K-depleted (22.9 +/- 4.4 pg/mg) and normokalemic (23.6 +/- 2.3 pg/mg) rats. Indomethacin significantly and comparably lowered prostaglandin content in both K-depleted and normokalemic rats. These studies, therefore, reveal no enhancement of prostaglandin synthesis with K depletion and demonstrate that the renal concentrating defect of K depletion in the rats is prostaglandin independent.
Improved renal cortical tubule suspension: spectrophotometric study of O2 delivery
Authors: Balaban R. S. , Soltoff S. P. , Storey J. M. , Mandel L. J.
Published: December 2017

An improved cortical tubule suspension from the rabbit kidney is described that contains almost entirely proximal convoluted tubules with little contamination by cellular debris or glomeruli. These tubules appear to be capable of active transepithelial transport, since their tubular lumina are open and ouabain inhibits 70% of the QO2. In previous preparations with closed tubular lumina, ouabain inhibited QO2 only 40% and the base-line QO2 was one-half to one-quarter that of the present preparation. The delivery of oxygen to this tubule suspension was compared to that of slices by three different means: oxygen consumption kinetics, ATP content, and, more directly by spectrophotometric monitoring of the redox state of cytochrome oxidase. Results demonstrate that the cortical slice is evidently oxygen deficient even when the bath PO2 is in excess of 570 mmHg. In contrast, the tubule suspension is shown to be adequately oxygenated even at a bath PO2 of 10 mmHg. This tubule suspension will be highly applicable for the analysis of aerobic metabolism in a functionally intact renal preparation by optical, electrode, and biochemical assay technologies.
Physiological evaluation of the isolated perfused rat kidney
Authors: Maack T.
Published: December 2017

A critical evaluation of the functional properties of the isolated perfused rat kidney is necessary to assess the usefulness of the preparation for renal function studies. Clearance and micropuncture experiments in isolated perfused rat kidneys perfused with a plasmalike medium containing 7.5 g/100 ml albumin, glucose, and amino acids show that proximal convoluted tubule functions are well preserved. Proximal convoluted tubule reabsorption of organic substances, electrolytes, and fluid is near normal, the latter being directly related to the peritubular oncotic pressure. Superficial single nephron glomular filtration rate and glomerular permselectivity are also preserved. However, abnormalities in renal hemodynamics, urinary concentration-dilution, and excretion of fluid and electrolytes persist even in the best preparations. High renal perfusate flow, due mainly to the low viscosity of the perfusate, and altered distal nephron functions explain at least in part these abnormalities. Therefore, the isolated perfused rat kidney is a useful preparation to particularly study glomerular and proximal convoluted tubule functions. Recent development of a nonfiltering isolated perfused rat kidney model, with preserved renal perfusate flow and cellular integrity, also permits the study of transport and metabolic functions of proximal tubular cells independently of luminal events.
Pathogenesis of renal hyperchloremic acidosis resulting from dietary potassium restriction in the dog: role of aldosterone
Authors: Hulter H. N. , Sebastian A. , Sigala J. F. , Licht J. H. , Glynn R. D. , Schambelan M. , Biglieri E. G.
Published: December 2017

In dogs dietary K+ restriction (16 days) results in diminished urinary net acid excretion (NAE) and systemic hyperchloremic metabolic acidosis (sigma delta NAE, -200 meq; delta[HCO3-]p, -2.9 +/- 0.3 meq/liter, P less than 0.05). Urinary aldosterone (aldo) excretion decreased by 34 +/- 3% (P less than 0.001) and metabolic clearance rate of aldo increased by 80 +/- 17% (P less than 0.02) during K+ restriction. Daily subcutaneous injection of a small amount of exogenous aldo (20 micrograms) during K+ restriction significantly attenuated the reduction in NAE (sigma delta NAE -51 vs. -200 meq, P less than 0.05) without raising plasma aldo concentrations to levels greater than control. These findings suggest that hypoaldosteronism induced by potassium depletion is at least in part the cause of the observed renal tubular acidosis. In adrenalectomized (ADX) dogs maintained on fixed mineralocorticoid and glucocorticoid replacement (aldo dose 60 micrograms/day), K+ restriction resulted in a significant degree of renal metabolic acidosis (delta[HCO3-]p, -1.4 +/- 0.3 meq/liter, P less than 0.01). In these ADX dogs, the exogenous supply of aldo was fixed but hypoaldosteronism may have developed owing to increased metabolic clearance rate of aldo caused by dietary K+ depletion. When mineralocorticoid replacement was withheld in ADX dogs, the steady-state degree of renal metabolic acidosis was no more severe in animals with preexisting dietary K+ depletion (16 days) than in the same animals when mineralocorticoid was withheld without preexisting K+ depletion. Thus, when neither endogenous nor exogenous aldo is present, K+ depletion does not result in a renal acidosis-producing effect that exacerbates that of aldo deficiency. The results of these studies suggest that the reduction in NAE and consequent metabolic acidosis induced by dietary K+ depletion is at least in part a consequence of aldo deficiency, and provide no evidence of an additional defect in acidification not caused by aldo deficiency.
Role of glucocorticoids and aldosterone in maintenance of colonic cation transport
Authors: Bastl C. P. , Binder H. J. , Hayslett J. P.
Published: December 2017

Adrenalectomized rats were maintained on physiologic replacement doses of aldosterone or dexamethasone for 24 h after adrenalectomy. Net cation movement and transmural potential difference were determined during in vivo perfusion of the colon. Adrenalectomy without replacement steroids resulted in marked reduction of sodium and water absorption, potassium secretion, and transmural potential difference (PD). Aldosterone 10 microgram . 100 g body wt-1 . 24 h-1 significantly increased net potassium secretion above adrenalectomized levels but did not restore transport to control levels. Sodium and water absorption and transmural PD were not affected. Aldosterone 30 microgram . 100 g body wt-1 . 24 h-1 increased but did not restore net movement of sodium or potassium to control levels. In contrast to aldosterone, physiologic amounts of dexamethasone, 10 microgram . 100 g body wt-1 . 24 h-1, preserved normal electrolyte movement and electrical properties in adrenalectomized rats. In additional experiments the aldosterone antagonist spironolactone was administered for 3 days to rats with intact adrenal function. Net sodium absorption fell only 22% below control with insigificant decreases in potassium secretion and transmural PD. These data suggest that glucocorticoid hormones exert regulatory control of basal colonic fluid and electrolyte function.
Effect of catecholamines on fluid reabsorption by the isolated proximal convoluted tubule
Authors: Bello-Reuss E.
Published: December 2017

The effect of L-norepinephrine and isoproterenol on fluid transport was studied in superficial convoluted segments and straight portions of the rabbit proximal tubule (PCT and PR, respectively) by the technique of microperfusion in vitro. In PCT, L-norepinephrine (10(-6) M) added to the bath stimulated reversibly fluid reabsorption (Jv) by about 67%. In the presence of propranolol (10(-4) M) in the bath, L-norepinephrine caused a small (about 19%) but significant decrease of Jv. Phentolamine and isoproterenol added simultaneously to the bath also increased fluid reabsorption, an effect that was abolished by propranolol. Norepinephrine had no effect on Jv when added to the perfusate in PCT. No change of Jv was observed after addition of norepinephrine to the bath in PR. The effects on fluid reabsorption rate observed in PCT are consistent with a physiologic role of the sympathetic nervous system in the modulation of PCT fluid transport.
Inorganic anion transport in kidney and intestinal brush border and basolateral membranes
Authors: Grinstein S. , Turner R. J. , Silverman M. , Rothstein A.
Published: December 2017

The efflux of inorganic anions from purified brush border and basolateral membrane vesicles from dog kidney cortex was measured under equilibrium exchange conditions. Marked differences in temperature sensitivity and effects of inhibitors were found between the Cl and SO4 transport pathways and between the two types of membranes. SO4 transport in both brush border and basolateral membranes was markedly reduced by cooling, but significant inhibition by 4,4'–diisothiocyano-2,2'–disulfonic stilbene (DIDS) was only observed in basolateral vesicles. In contrast, Cl efflux from both types of vesicles was neither substantially inhibited by DIDS nor by lowering the temperature to 0 degrees C. Phosphate efflux from basolateral membrane vesicles was found to be only partially sensitive to DIDS. Attempts to label the stilbene-sensitive SO4 pathway in basolateral vesicles using [3H2]DIDS as a marker were unsuccessful due to the nonspecific labeling of many membrane components. The asymmetry in inorganic anion transport behavior exhibited by brush border and basolateral membrane vesicles from dog renal proximal tubule was also observed in equivalent vesicles prepared from rat small intestine.
Effect of collagenase and ouabain on renal cell volume in hypotonic media
Authors: Linshaw M. A. , Grantham J. J.
Published: December 2017

Proximal straight tubules (S2 segments) swell rapidly in hypotonic media, but within a few minutes their volume returns toward control levels due to extrusion of K, Na, Cl, and water from the cytoplasm. In the present studies we determined the extent to which hydrostatic pressure (derived from the elastic tubule basement membrane (TBM) as the tubule enlarged in hypotonic medium) contributed to the regulation of cell volume. Removal of the TBM by collagenase had no effect on cell volume regulation in otherwise normal tubules. By contrast, tubules treated with ouabain, though they appeared to regulate their volumes in hypotonic media, were unable to do so in the presence of glycoside if the TBM had been removed with collagenase. This latter result is interpreted to show that hydrostatic pressure generated by extension of the TBM can cause “apparent” volume regulation when the sodium pump is blocked by ouabain. We conclude that normal proximal renal tubules regulate cell volume in hypotonic solutions by mechanisms that are dependent on the normal operation of the classical sodium pump.
Isolated nephron segments in a rabbit model of ischemic acute renal failure
Authors: Hanley M. J.
Published: December 2017

Renal artery occlusion has been extensively used in animal models to cause acute renal failure. The present isolated tubule microperfusion studies were designed to examine the transport characteristics of multiple nephron segments of the rabbit after 60 min of total renal ischemia. Preliminary studies showed that this maneuver produced significant and persistent elevations of serum creatinine. The tubules were perfused and bathed with artificial solutions simulating ultrafiltrate and studied at 37 degrees C. Four nephron segments were examined. Ischemia reduced proximal convoluted tubule fluid reabsorption 77% (0.72 +/- 0.11 vs. 0.14 +/- 0.06 nl . mm-1 . min-1, P less than 0.01) and cortical proximal straight tubule fluid reabsorption 88% (0.54 +/- 0.10 vs. 0.06 +/- 0.03 nl . mm-1 . min-1, P less than 0.005). Ischemia reduced the ability of the thick ascending limb of Henle's loop to lower perfusate chloride ion concentration 60% (-47 +/- 9 vs. -19 +/- 3 meq/liter, P less than 0.02) and its diluting ability 49% (-87 +/- 15 vs. -44 +/- 7 mosmol/kg H2O, P less than 0.01). Ischemia reduced the antidiuretic hormone-dependent osmotic water permeability of the cortical collecting tubule 59% (0.0203 +/- vs. 0.0083 +/- 0.0020 cm/s, P less than 0.01). Morphologic alterations were noted in the proximal segments but not in the distal segments of the nephron. The current studies demonstrate that 60 min of renal ischemia impairs the transport capability of all proximal and distal nephron segments studied.
Effects of glucocorticoid steroids on renal and systemic acid-base metabolism
Authors: Hulter H. N. , Licht J. H. , Bonner E. L. , Glynn R. D. , Sebastian A.
Published: December 2017

Clinical states of hyperglucocorticoidism are associated with renal metabolic alkalosis, yet the systemic and renal acid-base response to chronic administration of glucocorticoid steroids (dexamethasone, triamcinolone) possessing little or no mineralocorticoid activity has not been investigated. In balance studies studies in dogs administration of triamcinolone (Tcn), 1.0 mg. kg-1. day-1 for 6–9 days (group I, n = 5), resulted in a persistent reduction in urine pH and increase in net acid excretion (NAE), and in the excretion of urinary unmeasured anions (C+NH4,Na;K minus A-Cl,HCO3,Pi), which were identified as organic anions and sulfate. A significant degree of metabolic acidosis occurred initially (delta [HCO3-]p, -3.4 meq/liter, P less than 0.05, day 1). As Tcn administration was continued, the cumulative increment in net acid excreted exceeded the cumulative increment in urinary unmeasured anion excreted and [HCO-3]p returned to pre-Tcn control values and remained stable thereafter. In the steady state of Tcn administration plasma potassium concentration and renal potassium clearance were not significantly different from pre-Tcn control, in contrast to the findings of hypokalemia and increased renal potassium clearance during chronic administration of deoxycorticosterone (DOC). Triamcinolone did not result in antinatriuresis or antichloruresis. Chronic administration of a 10–fold smaller dose of Tcn (0.1 mg . kg-1 . day-1) in an additional group (group III) also resulted in a persisting reduction in urine pH and an increase in net acid excretion that exceeded unmeasured anion excretion and resulted in a small increase in steady-state plasma bicarbonate concentration. These results suggest that chronic administration of potent glucocorticoid steroids results in 1) a persisting increase in endogenous acid production, and 2) stimulation of renal hydrogen ion secretion that was of greater degree than accounted for by the increment in endogenous acid production and that was not accompanied by renal mineralocorticoid effects on sodium and potassium transport.
Loop of Henle during the water-to-antidiuresis transition in Brattleboro rats
Authors: Moore L. C. , Marsh D. J. , Martin C. M.
Published: December 2017

A mathematical model of the renal medulla predicted patterns of NaCl and urea concentration and flow rate when a rat undergoing water diuresis receives antidiuretic hormone (ADH), We tested these predictions with micropuncture and clearance experiments in Brattleboro rats lacking endogenous ADH. The model successfully predicted urine flow rate, urea excretion rate, and ascending vasa recta (AVR) solute concentration patterns. A novel result the model correctly foresaw was that AVR urea concentration lagged behind NaCl, because ADH temporarily interrupted urea recycling. The model suggested that this lag would be carried over to descending limb of Henle's loop (DLH) fluid only if DLH permeabilities allowed solutes as well as water to move across the DLH wall, but not if solute movement was negligible. Experimental results showed the lag, therby suggesting significant solute entry into DLH fluid during the transition, and, by extension, in other conditions as well, As shown in a companion paper (Am. J. Physiol. 239 (Renal Fluid Electrolyte Physiol. 8): F57–F71, 1980), solute permeation across DLH limits hypertonic urine formation in the inner medulla unless thin ascending limbs perform active transport of NaCl.
Differential renal effects of cyclooxygenase inhibition in sodium-replete and sodium-deprived dog
Authors: Blasingham M. Cynthia , Nasjletti Alberto
Published: December 2017

We studied the renal effects of the cyclooxygenase inhibitor sodium meclofenamate (M) (5 mg/kg, iv) in the pentobarbital-anesthetized dog that had been maintained on an elevated (100 meq/day) or on a reduced (<5 meq/day) sodium intake, and during the administration of angiotensin II in the sodium-replete dog, or the angiotensin receptor blocker [Sar1–Ala8]angiotensin II in the sodium-deprived dog. In the sodium-replete dog, M did not affect mean arterial blood pressure (MABP), renal blood flow (RBF), glomerular filtration rate (GFR), or urine volume (V), but reduced the urinary excretion of sodium (UNa V) by 47%, and of immunoreactive PGE2 (iPGE2) by 90%. However, in the sodium-replete dog during angiotensin II infusion (3 ng · kg-1 · min-1, iv), M reduced RBF by 35%, GFR by 24%, V by 71%, and iPGE2m by 94%. Similarly, in the sodium-deprived dog M reduced RBF by 34%, GFR by 28%, and iPGE2 excretion by 89%. However, M did not affect RBF or GFR in the sodium-deprived dog during infusion of [Sar1-Ala8]angiotensin II (6 μg · kg-1 · min-1, iv), although iPGE2 excretion was reduced by 84%. This study demonstrates that the effects of M on renal hemodynamics in the dog vary with the state of sodium balance and suggests that a prostaglandin(s) contributes to maintenance of renal blood flow during activation of the renin-angiotensin system.

meclofenamate; renal prostaglandins; renin-angiotensin system; receptor blocker; renal hemodynamic and excretory function

Submitted on October 17, 1979

Accepted on May 9, 1980
Basal norepinephrine overflow into the renal vein: effect of renal nerve stimulation
Authors: Oliver Juan A. , Pinto John , Sciacca Robert R. , Cannon Paul J.
Published: December 2017

In order to determine whether the fraction of norepinephrine released from the renal nerves that escapes into the circulation can be used an an index of renal sympathetic nervous activity, arterial and renal vein plasma norepinephrine concentrations were measured by a radioenzymatic technique along with renal blood flow in anesthetized dogs under control conditions and during electrical renal nerve stimulation. In 25 animais studied under conditions of normal sodium balance, plasma norepinephrine in the renal vein, 198 ± 26 pg/ml, was significantly higher than in arterial blood, 102 ± 10 pg/ml (P < 0.001). In five dogs, electrical stimulation of the renal nerves (12 V, 3 ms) at frequencies of 0.5, 2,6, 12, and 18 Hz for 1 min was associated with increased norepinephrine concentration in renal venous plasma and an increase in the calculated renal norepinephrine overflow. There was a significant linear relationship between the frequency of stimulation and norepinephrine overflow into the renal vein in each animal, but there was also a significant interanimal variation in the slope of this relationship (P <0.01). Electrical stimulation at a frequency of 2 Hz significantly decreased renal blood flow (-24 ± 7 ml/min, P < 0.01). The maximal effect was achieved at 6 Hz (-66 ± 11 ml/min). The data indicate that there is a base-line overflow of norepinephrine into the renal venous blood of the dog that increases with increasing frequency of electrical nerve stimulation. They suggest that measurements of norepinephrine overflow into the renal vein may be used to assess the activity of the renal sympathetic nervous system.

renal blood flow; catecholamines; renin; dog

Submitted on January 10, 1980

Accepted on April 29, 1980
Secretion of urate in the proximal convoluted tubule of the rat
Authors: Weinman E. J. , Sansom S. C. , Steplock D. A. , Sheth A. U. , Knight T. F. , Senekjian H. O.
Published: December 2017

In order to examine the transepithelial secretory flux of urate in the rat proximal tubule, simultaneous perfusions of capillaries and lumens were performed. The capillary perfusate contained [2–14C]urate in concentrations of 0.305–2.941 mM. The secretory flux of urate increased as the concentration of urate in the capillary perfusion solution was increased from 0.305 to 1.235 mM but tended toward a plateau at higher concentrations. An apparent Km of 0.41 mM and Vmax of 4.7 pmol·min-1·mm-1 were calculated from the observed net flux and an estimated passive permeability coefficient of 0.725 pmol·min-1·mm-1. The addition of probenecid (10-4 M) to the capillary perfusion solution inhibited urate secretion in a manner consistent with that of a competitive inhibitor. The addition of p-chloromercuribenzoate (10-4 M) to the capillary perfusion solution inhibited the Vmax but not the Km, suggesting a non-competitive type of inhibition. These data provide the first estimates of the apparent transport constants for urate secretion in the rat proximal tubule determined in vivo. Urate secretion is mediated by a saturable carrier-mediated system. This carrier is not affected by the presence or absence of potassium in the perfusion solution but can be inhibited by the addition of either probenecid or p-chloromercuribenzoate.

high-performance liquid chromatography with electrochemical detection; renal micropunction; organic acid secretion

Submitted on March 5, 1980

Accepted on April 25, 1980
Electrical characteristics of snake distal tubules: studies of I-V relationships
Authors: Koeppen B. M. , Beyenbach K. W. , Dantzler W. H. , Helman S. I.
Published: December 2017

Distal tubules of Thamnophis spp. were perfused in vitro with Ringer solution containing either 16 or 150 mM Na and bathed with 150 mM Na Ringer. Current-voltage relationships were obtained by injecting pulses of constant current, Io, into the tubule lumen and recording changes in voltage, delta Vo, at the proximal end of the perfused tubule segment. The Io-Vo plots showed a distinct break at a voltage E1 (approximately 85 mV) that was greater than the open-circuit voltage, VToc, and similar to values of ENa, the transepithelial driving force for Na transport estimated by other methods. The resistance of the shunt pathway, Rs, was estimated from the values of the transepithelial resistance after luminal addition of 10(-5) M amiloride, which caused a rapid fall of the VToc to 0 mV with concurrent increases of the transepithelial resistance. These estimates of Rs were the same as the values of E1/I1 obtained from the Io-Vo plots. The VToc, RT, and Rs were independent of the bath [Na] and were not influenced by the addition of amiloride to the bath. As in frog skin and toad urinary bladder, the ENa and Rs of the snake distal tubule can be estimated from studies of their Io-Vo plots, and the E1 appears to be independent of the transepithelial chemical potential for Na.
Osmolar influences on urinary acidification and metabolism in the Colombian toad bladder
Authors: Favre H. , Hwang K. H. , Bourgoignie J. J.
Published: December 2017

An increase in the osmolarity of the serosal fluid bathing the isolated toad bladder inhibits sodium transport across the preparation. Opposite effects occur with a decrease in serosal Ringer osmolarity. The present experiments investigate the specificity of these osmolar effects by examining the role of extracellular fluid tonicity on the acidification capacity of the isolated Colombian toad bladder. Acidification, estimated by the reversed short-circuit current (RSCC) developing across the Colombian toad bladder in the absence of sodium transport, was stimulated by serosal hypotonicity and inhibited by serosal hypertonicity of acetazolamide. Changes in the mucosal Ringer tonicity had no effect on RSCC. A direct correlation was found between the acidification process and the rate of oxidation of [14C]pyruvate by quarter-bladders exposed to changes in extracellular fluid osmolarity in the presence of amiloride. The osmolar effects on RSCC may result from changes in cell metabolism.
Interaction of the prostaglandin and renin-angiotensin systems in isolated rat glomeruli
Authors: Beierwaltes W. H. , Schryver S. , Olson P. S. , Romero J. C.
Published: December 2017

Renal glomeruli were isolated from rat kidneys using a passive mechanical sieving technique. Suspensions of 40–50 mg glomeruli were placed in glass chambers and superfused by a modified Krebs-Ringer solution. Effluent collections of 10-min fractions were measured for renin or prostaglandin (PG) E2 concentration using radioimmunoassays. The perfusate was altered to contain either the beta-adrenergic agonist isoproterenol, angiotensin II, or arachidonic acid. Isoproterenol at 1.78 or 8.1 X 10(-4) M produced a significant release of renin, but the concentration of PGE2 was unaffected. Isoproterenol-stimulated renin release was blocked by 1.2 X 10(-4) M propranolol but was unaffected by 6.3 X 10(-6) M meclofenamate. Angiotensin II at 4 or 40 X 10(-9) M altered neither renin nor PGE2. Arachidonic acid administered at 1.6 or 16.0 X 10(-5) M produced a marked increase in PG synthesis and stimulated a significant release of renin. Treatment of glomeruli with 6.3 X 10(-6) M meclofenamate attenuated PGE2 synthesis and abolished renin release, but 1.2 X 10(-4) M propranolol had no effect on PG synthesis or the coincident release of renin. These results give direct evidence of an interrelating mechanism between renal prostaglandins and renin release that is independent of external tubular or hemodynamic stimuli and show that the beta-adrenergic pathway of renin stimulation is independent of any modifying influence exerted by prostaglandins.
Renal venous portal contribution to PAH and uric acid clearance in the chicken
Authors: Shideman J. R. , Evans R. L. , Bierer D. W. , Quebbemann A. J.
Published: December 2017

The contributions of the renal venous portal and the renal arterial circulations to the renal clearance of p-aminohippuric acid (PAH) and uric acid were determined in the unanesthetized chicken by the simultaneous use of the urinary clearance technique and the Sperber preparation. The [3H]PAH apparent tubular excretion fraction (ATEF) and the clearance of inulin (CIn) were used as indicators of the renal portal and renal arterial contributions, respectively, in a planar equation for total PAH clearance. This equation accurately reflects the renal clearance of PAH as well as the renal venous portal and renal arterial contributions to the total renal clearance of PAH. The equation suggests that under normal conditions approximately 50% of the renal clearance of PAH or uric acid comes from the renal venous portal circulation, with the remaining 50% coming from the arterial circulation. An inverse hyperbolic relationship between the filtration fraction (CIn/CPAH) and the [3H]PAH ATEF was found, demonstrating that the filtration fraction in the chicken decreases from a value of 18 to approximately 6% as the renal portal plasma flow increases from zero to a maximum value. Our equation for total clearance was also used with results of experiments on inhibition of uric acid excretory transport by L- and D-dopa and by probenecid to locate the probable sites of action of those inhibitors.
Calcium in the control of renin secretion: Ca2+ influx as an inhibitory signal
Authors: Park C. S. , Han D. S. , Fray J. C.
Published: December 2017

The mechanism for the inhibition of renin secretion in vitro from renal cortical slices by angiotensin II, antidiuretic hormone, ouabain, and high K+ concentration was studied. The inhibitory effect of these agents was blocked by a Ca antagonist, verapamil. In addition, epinephrine stimulated renin secretion and its stimulatory action was blocked by ouabain. These results support the hypothesis that Ca2+ influx into juxtaglomerular cells plays a role as an inhibitory signal whereas Ca2+ efflux is a stimulatory signal for renin secretion. Renin secretion was greatly stimulated by lowering incubation temperature, indicating that renin secretion is not energy dependent. The possibility is discussed that Ca2+ of juxtaglomerular cells might activate an enzyme(s) that then modulates some sequential steps of renin secretory processes, thereby controlling the rate of renin secretion.
Sites of hormone action in the mammalian nephron
Authors: Morel F.
Published: December 2017

Hormone-dependent adenylate cyclase activity was measured separately in the different nephron portions by combining the microdissection of collagenase-treated rabbit kidneys and the use of a single tubule enzyme microassay. The results obtained in the rabbit for vasopressin, parathyroid hormone, calcitonin, and isoproterenol are given and discussed. Each hormone stimulated adenylate cyclase activity in several well-localized segments of tubule according to a highly specific and reproducible pattern. Sharp transitions were generally noted between responsive and unresponsive nephron portions. In the rat kidney, the functional segmentation of the distal convoluted tubule was not as clearly delineated as in the rabbit kidney. Various nephron segments of the rat kidney were observed to contain glucagon-sensitive adenylate cyclase activity. When the results obtained for vasopressin are compared in rabbit, rat, mouse, and human kidneys, species differences are noted with respect to the responsiveness to arginine vasopressin in the medullary portion of thick ascending limbs of Henle's loops. It is concluded that biochemical approaches can be used as a means of investigating problems dealing with kidney physiology very near the cell level.
Effects of glomerular filtration dynamics on the glomerular permeability coefficient
Authors: Tucker B. J. , Blantz R. C.
Published: December 2017

Studies were performed in Munich-Wistar rats (n = 24) to determine if the glomerular permeability coefficient (LpA) is affected by changes in the systemic oncotic pressure (pi A) as well as other determinants of glomerular filtration [nephron plasma flow (RPF) and glomerular hydrostatic pressure gradient (delta P)] and systemic hematocrit (Hct). Multiple regression analysis was used to separate the respective relationships of pi A, delta P, RPF, and Hct to LpA to ascertain whether the correlation of LpA to these variables was direct or mediated by some concurrently changing factor. Three two-period protocols were used to examine the changes of these determinants of filtration: 1) hydropenia to 10% body wt saline expansion (SE), 2) SE to 1% body wt of concentrated rat plasma protein (25 g/100 ml) solution (HP) with removal of 1.5% body wt whole blood, and 3) SE to 1% body wt HP with 2.5% body wt whole blood removed with reinfusion of the removed erythrocytes. Changes in LpA correlated directly with changes in pi A (P less than 0.01) and inversely with delta P (P less than 0.01). There was no direct correlation of LpA to RPF or consistent correlation of LpA to Hct.
Handling of insulin by the isolated perfused rat kidney
Authors: Maude D. L. , Handelsman D. G. , Babu M. , Gordon E. E.
Published: December 2017

The organ clearance of insulin calculated from the rate of disappearance of immunoreactive insulin from the perfusate averages 0.76 ml.min-1.g kidneys wt-1, a value greater than the simultaneously measured glomerular filtration rate. Clearance does not fall when hormone concentration is as high as 7 X 10(-8) M (10,000 microunits/ml). Fifteen percent of the cleared insulin is excreted in the urine; the remainder is chemically modified and appears in the perfusate both as low molecular weight fragments and as high molecular weight species. In the process of clearing the hormone, kidney tissue accumulates both intact insulin and 125I-labeled insulin degradation products. the organ clearance of insulin is not curtailed when the glomerular filtration rate is sufficiently reduced (by lowering perfusate pressure) to cause urine flow to cease. Studies using hyperglycemic perfusates and kidneys taken from starving or streptozotocin-diabetic animals provided no evidence that the kidney plays a role in the regulation of plasma glucose by modulating the rate of insulin degradation.