bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic mechanisms in CNS-induced natriuresis in the conscious rat
Authors: Bealer S. L.
Published: December 2017

These experiments were designed to determine 1) the effects of increased CSF sodium concentration on renal hemodynamics in the conscious rat, and 2) the role of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) in the natriuretic and hemodynamic responses during this treatment. After electrolytic lesions of AV3V periventricular tissue or control surgery, blood pressure, glomerular filtration rate, effective renal blood flow, urine volume, and sodium and potassium excretion were measured before and during intraventricular (IVT) infusion of either isotonic or hypertonic saline solutions in conscious hydrated rats. Blood pressure, glomerular filtration rate, and sodium and potassium excretion increased during IVT infusion of concentrated sodium solutions in control rats but not in animals with lesions in the AV3V region. These data support the hypothesis that the natriuretic response to increased CSF sodium concentration in the rat is due to a pressor response and/or increased glomerular filtration rate and demonstrate that ablation of AV3V periventricular tissue blunts the natriuretic response, possibly through diminished central pressor mechanisms and/or decreased central control of glomerular filtration rate.
Evaluation of xenon-133 renal blood flow measurement in the intact rat
Authors: Butt T. J. , Jones D. R. , Wallis A. T. , Simpson F. O.
Published: December 2017

The xenon-133 method for measuring renal blood flow in the intact rat was evaluated by direct measurement using a nonhemolyzing pump to perfuse kidneys in situ with the rat's own blood. Flows were calculated from the xenon data by means of four commonly used types of analysis: compartmental analysis using the weighted arithmetic mean (WAM), compartmental analysis using the weighted harmonic mean (WHM), stochastic analysis (SA), and initial slope analysis (ISA). WHM and SA estimate actual blood flows, whereas WAM and ISA provide only an index of mean renal flow. All results correlated well with the pumped flows (r values ranged from 0.79 to 0.98). However, the various types of analysis gave a wide range of calculated flows. This may explain some of the variation found in mean renal flow values reported in the literature. The method of choice was WHM, using only the first two compartments; the regression line between this (y) and direct measurement (x) was y = 0.98x + 0.17, r = 0.96.
Glomerular filtration dynamics during renal vasodilation with acetylcholine in the dog
Authors: Thomas C. E. , Ott C. E. , Bell P. D. , Knox F. G. , Navar L. G.
Published: December 2017

The reason for the failure of glomerular filtration rate (GFR) to exhibit plasma flow dependency during pharmacologic vasodilation remains unclear although it has been suggested on the basis of experiments in rats that vasodilators may lead to a reduction in the glomerular filtration coefficient (Kf). To evaluate the applicability of this hypothesis to the dog, the effects of vasodilation with acetylcholine on glomerular dynamics and Kf were evaluated in two groups of dogs. One group (n = 19) was studied at spontaneous arterial pressures to allow maximum vasodilation to occur. In the other group (n = 5), renal arterial pressure was reduced and maintained at approximately 89 mmHg. Glomerular filtration rate and single nephron glomerular filtration rate were not altered significantly during acetylcholine infusion in either of the two groups. Both whole kidney and superficial filtration fractions decreased significantly. At spontaneous arterial pressures, transglomerular hydrostatic pressure was not altered significantly because of equivalent increases in proximal tubule pressure and in glomerular pressure. In the dogs studied at reduced renal perfusion pressure, glomerular capillary pressure did not change, but proximal tubule pressure increased slightly. Average effective filtration pressures and Kf were not significantly altered during the infusion of acetylcholine either at spontaneous or reduced renal perfusion pressures. These observations indicate that Kf in the dog is not significantly decreased by acetylcholine and that GFR is not affected during infusion of this agent because the effective filtration pressure is not significantly altered.
Urea transport in nephron segments from medullary rays of rabbits
Authors: Knepper M. A.
Published: December 2017

To evaluate possible routes of urea delivery to the renal medulla, urea transport was studied in cortical thick ascending limbs and proximal straight tubules dissected from inner cortical medullary rays of rabbit kidneys. Urea was measured colorimetrically in the perfused, collected, and bath fluids. No evidence for active transport of urea was found in either segment. With imposed urea concentration differences between perfusion and bath fluids, there were significant passive fluxes of urea in both segments. The magnitude of the flux was independent of the direction of the concentration difference. Apparent permeability coefficients (X10(-5) cm/s) for urea were 2.0 for the cortical thick ascending limbs and 1.5 for the proximal straight tubules. Based on the measured permeability in the cortical thick ascending limb, substantial passive absorption of urea is predicted in vivo. This will contribute to the dilution of tubular fluid in this segment. The results in proximal straight tubules are compatible with passive urea secretion but not with a significant degree of active secretion.
Action of adenosine on cyclic 3',5'-nucleotides in glomeruli
Authors: Abboud H. E. , Dousa T. P.
Published: December 2017

Recent in vivo studies indicated that adenosine has a profound effect on glomerular dynamics and renal circulation. Because its effect in nonrenal tissues is frequently mediated by adenosine 3',5'-cyclic monophosphate (cAMP), we examined adenosine's effect on cyclic nucleotides in rat kidney. Incubation of tissue slices from renal cortex or medulla with 0.1 mM adenosine resulted in marginal or no increase in cAMP. In isolated glomeruli, adenosine caused a marked and dose-dependent (10(-6) to 10(-4) M) increase in cAMP accumulation. Inosine, a deaminated metabolite of adenosine, had no effect on cAMP levels in glomeruli. No distinct effect of adenosine on cAMP was observed in cortical tubules under the same testing conditions. An increase in cAMP levels in glomeruli elicited by adenosine was blocked by theophylline, a known inhibitor of adenosine receptors. In contrast, theophylline enhanced rather than decreased the stimulation of cAMP accumulation in glomeruli by serotonin. Dipyridamole, a proposed inhibitor of cellular uptake of adenosine, did not inhibit but rather enhanced cAMP accumulation in glomeruli in response to adenosine. In the present experiments adenosine did not influence guanosine 3',5'-cyclic monophosphate levels in either glomeruli or other tested preparations of renal tissue. These results provide the first experimental evidence that adenosine stimulates cAMP accumulation in glomeruli and suggest that this effect is probably due to action on the adenosine receptor on the cell surface. Our observations raise the possibility that some of the effects of adenosine in glomerular cells may be mediated via cAMP accumulation.
Effect of osmotic shocks on rabbit kidney cortex slices
Authors: Gilles R. , Duchene C. , Lambert I.
Published: December 2017

Rabbit kidney cortex slices behave an osmometers when withstanding hyperosmotic or hyposmotic shocks of amplitude up to pi 1/pi 2 = 1.25. For hyposmotic shocks of amplitude larger than or equal to pi 1/pi 2 = 1.50, the maximum swelling achieved is less than what can be expected on the basis of the van't Hoff relation, thereby indicating that a volume regulation process is taking place. Volume regulation in kidney slices can be dissociated into two distinct phases. The first one, of swelling limitation, is very rapid and keeps maximum cell volume at values lower than expected when the tissue is considered as an osmometer. This phase is followed by a slow volume readjustment process during which volume progressively decreases towards control values. The major intracellular osmotic effector loss during both swelling limitation and volume readjustment is Na+. The overall volume regulation process is insensitive to furosemide, vanadate, and bumetanide. Swelling limitation is blocked by addition of ouabain. Contrary to what has been believed previously, there is, however, no need to implicate control of the activity of a ouabain-sensitive, Na+/K+ pump in the Na-dependent volume regulation mechanism.
Cell culture of renal epithelium derived from rabbit microdissected cortical collecting tubules
Authors: Currie M. G. , Cole B. R. , DeSchryver-Kecskemeti K. , Holmberg S. , Needleman P.
Published: December 2017

Cortical collecting tubules were dissected from rabbit kidney and cultured in a hormonally defined serum-free medium. Morphologic studies of the cultured cells derived from the collecting tubule indicated that the cells maintained their epithelial nature. These studies also revealed the presence of two distinct cell types that closely resemble the principal and intercalated cell types of the cortical collecting tubule. Several biochemical characteristics of the cultured cells were found to be similar to previously reported values for the cortical collecting tubule. The cells retain hormonal responsiveness to antidiuretic hormone (ADH), as demonstrated by a 12-fold increase in cAMP in response to ADH. Cultured cortical collecting tubule cells produce prostaglandins, with prostaglandin E2 as the predominant cyclooxygenase product. This study presents the first morphologic and biochemical characterization of cortical collecting tubule epithelial cells grown in culture.
Video measurement of basolateral membrane hydraulic conductivity in the proximal tubule
Authors: Welling L. W. , Welling D. J. , Ochs T. J.
Published: December 2017

Isolated, lumen-collapsed S1, S2, and S3 proximal tubule segments from the rabbit were exposed acutely to media made hypotonic or hypertonic by adjusting the concentration of the impermeant solute raffinose. The result was a water flux into or out of the cells across their basolateral cell membranes and a consequent swelling or shrinking of the cells. From tubule volume changes measured at 1/60-s intervals during the first 0.03-0.2 s of video recordings, the earliest water fluxes were found to be 0.76 +/- 0.04 nl X min-1 X mm-1 X mosM-1 in S1, 0.53 +/- 0.03 in S2, and 0.35 +/- 0.04 in S3. When normalized to outer tubule surface areas, these fluxes yield statistically different hydraulic conductivities of about 5,500, 4,000, and 3,000 microns X s-1 in the three segments. However, when normalized to the basolateral membrane surface areas, the basolateral membrane hydraulic conductivities are all approximately 300 microns X s-1 and not statistically different. If one assumes that the hydraulic conductivities of the basolateral and apical cell membranes are equal, the latter value agrees with reported transtubular measurements and is sufficient to allow nearly isotonic transcellular absorption to occur with driving forces of 2-3 mosM.
Autoregulation in vasa recta of the rat kidney
Authors: Cohen H. J. , Marsh D. J. , Kayser B.
Published: December 2017

Vasa recta blood flow autoregulation was studied by measuring flow velocity in individual vessels on the papilla surface with a video adaptation of the dual-slit erythrocyte velocity method. Vessel diameter did not vary with arterial pressure in the range of 60-150 mmHg, allowing the calculation of the ratio of flows in a single vessel at two pressures from the ratio of velocities. Flow velocity in single vasa recta increased with arterial pressure to 75 mmHg, remained constant in the range of 75-125 mmHg, and increased with higher pressures. In a second series of animals, whole kidney blood flow auto-regulated above 90 mmHg. Vasa recta and whole kidney flow patterns were not changed by extracellular fluid volume expansion. Volume expansion caused a greater increase in ascending than in descending vasa recta flow, reflecting the volume load from enhanced collecting duct reabsorption in diuresis. In a final series, Na excretion varied with arterial pressure in the range of 90-130 mmHg. Because vasa recta velocity remains constant within this range, pressure diuresis cannot be caused by the lack of autoregulation of vasa recta blood flow, at least to 130 mmHg.
Demonstration of active potassium secretion in the late distal tubule
Authors: Jones S. M. , Hayslett J. P.
Published: December 2017

Studies were performed in the rat, under steady-state conditions, to determine the mode of potassium transport in the late distal tubule. In these experiments the potential difference and potassium activity were measured simultaneously in steady-state fluid droplets in control rats, during acute infusion of KCl, and in potassium-deficient rats. The results demonstrate active potassium secretion in the late distal tubule of the control and KCl-infused animals, since the observed potassium activity of 11.14 +/- 1.39 in control animals and 25.26 +/- 2.96 meq/liter in potassium-loaded animals was significantly greater than the predicted values of 7.75 +/- 0.59 and 14.01 +/- 0.94 meq/liter in the same groups, respectively. In potassium-deficient animals, however, the observed potassium activity in luminal fluid of 4.03 +/- 0.55 meq/liter was not different from the predicted value of 4.26 +/- 0.32. In summary, this study demonstrates that potassium secretion in the late distal tubule of the rat occurs by an active process and fails to demonstrate active absorption in the same tubular segment.
Metabolic acidosis and parathyroidectomy increase Na+-H+ exchange in brush border vesicles
Authors: Cohn D. E. , Klahr S. , Hammerman M. R.
Published: December 2017

Na+-H+ exchange across the brush border membrane of the renal proximal tubular cell is a mechanism for Na+ reabsorption and H+ secretion. An electroneutral Na+-H+ exchange activity has been identified in isolated renal brush border membrane vesicles from rat and dog kidney, and increased Na+-H+ exchange has been measured in brush border membrane vesicles from remnant kidneys of dogs with chronic renal failure. To ascertain whether changes in H+ secretion by the kidney observed in chronic metabolic acidosis and in states of altered parathyroid function might result from altered Na+-H+ exchange across the renal cortical cellular brush border membrane, we measured Na+-H+ exchange in brush border membrane vesicles from kidneys of dogs with chronic metabolic acidosis and from kidneys of thyroparathyroidectomized dogs. Increased amiloride-sensitive Na+-H+ exchange was demonstrated in brush border membrane vesicles from kidneys of both groups of dogs, suggesting that adaptations in H+ excretion in chronic metabolic acidosis and hypoparathyroidism might be explained by increased activity of a renal brush border membrane Na+-H+ exchanger.
Chloride-depletion alkalosis with a normal extracellular fluid volume
Authors: Luke R. G. , Galla J. H.
Published: December 2017

Current concepts hold that volume expansion is essential to the correction of chloride-depletion alkalosis (CDA) with chloride repletion in a permissive role. In this scheme, intranephronal fluid reabsorption would be redistributed with increased delivery to the distal nephron where the provided chloride is readily reabsorbed and the limited capacity for bicarbonate reabsorption would promote bicarbonate excretion and correction of CDA. In a model of CDA produced by peritoneal dialysis against 0.15 M NaHCO3, we have shown complete correction of CDA within 24 h without volume expansion by either oral isotonic sodium or chloride salts with 70 mM chloride and despite an obligatory bicarbonate load and negative sodium and potassium balance. During correction of CDA without volume expansion in rats by intravenous isotonic fluids containing 80 mM chloride, fractional fluid and chloride reabsorptions in the proximal convoluted tubule and in the loop segment of superficial nephrons were not different from controls but chloride reabsorption was enhanced in the collecting duct segment and probably within the distal convolution. Despite no differences in serial hematocrits, blood pressure, and measured plasma volume, kidney and nephron glomerular filtration rate (GFR) were reduced in CDA and returned to normal upon recovery 24 h later.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldosterone response in the turtle bladder is associated with an increase in ATP
Authors: Cortas N. , Abras E. , Walser M.
Published: December 2017

Urinary bladders from freshwater turtles, mounted as sacs, were stripped of their serosa and submucosa. This did not alter conductance. They were maintained in open circuit except for brief observation of short-circuit current (SCC) every 15 min. Potential difference (PD) averaged 68 +/- 14 mV and SCC 485 +/- 100 microA. Acetazolamide 10(-3) M increased SCC by 46 +/- 27 microA. Aldosterone 10(-7) M following acetazolamide resulted in a rise in SCC that began at about 75 min and reached a plateau between 3 and 5 h. SCC rose 127 +/- 15% compared with control bladder halves. ATP measured in perchloric acid extracts 5 h after addition of aldosterone increased by 33% (P less than 0.01) and (ATP)/(ADP) X (Pi) by 81% (P less than 0.01). These results support the view that the stimulatory effects of aldosterone on active sodium transport involve an increase in ATP and (ATP)/(ADP) X (Pi).
Renal perfusion in dogs with experimental hepatic cirrhosis: role of prostaglandins
Authors: Levy M. , Wexler M. J. , Fechner C.
Published: December 2017

Increased renal production of prostaglandins are thought to be important for the maintenance of kidney blood flow in advanced cirrhosis. In alert, unanesthetized dogs with chronic cirrhosis and ascites, produced by bile duct ligation, we measured inulin and p-aminohippurate (PAH) clearance before and after the intravenous administration of 2 mg/kg indomethacin, an inhibitor of prostaglandin production. Inulin and PAH clearance declined by 42 and 43%, respectively. This decline in renal perfusion was not associated with changes in blood pressure or cardiac output. If portal hypertension was prevented by creating an end-side portacaval anastomosis at the time of bile duct ligation, indomethacin was without effect on renal perfusion whether or not the dog had ascites. If ascites was completely mobilized in cirrhotic dogs with portal venous hypertension with the aid of a LeVeen valve, indomethacin depressed inulin and PAH clearance as usual during the steady-state period once all ascites had been removed. An attempt was made to determine some of the factors mediating the apparent increase in renal prostaglandin synthesis by administering various pharmacological antagonists. The inhibition of angiotensin effect with saralasin and the inhibition of kallikrein with aprotinin prevented the usual indomethacin effect. It is concluded that portal hypertension, but not a “sick liver per se, in cirrhosis activates the renin-angiotensin system to both produce renal vasoconstriction and stimulate prostaglandin synthesis, thereby normalizing renal perfusion. Renal kallikrein also appears to play a role, probably by augmenting renin release.
Evidence for PAH extraction from superficial cortical efferent vessel plasma
Authors: Weinstein S. W. , Klose R. , Kumar A. M.
Published: December 2017

Consistent with its anatomical association with the proximal tubule we have previously shown that superficial cortical efferent vessel blood contains an admixture of early and late proximal tubular reabsorbate. Since tubular secretion of p-aminohippurate (PAH) occurs predominantly in the late proximal tubule, extraction of this compound should occur preferentially from efferent vessel blood. As a result, the midportion of the proximal convoluted tubule supplied by the more downstream peritubular capillaries would receive blood containing a disproportionately reduced concentration of PAH. To study this, proximal and distal tubular fluid and efferent vessel blood samples were collected from rats. The data confirm that preferential secretion of PAH occurs in the pars recta and demonstrate that PAH is extracted from efferent vessel plasma by the pars recta. This in turn preferentially reduces PAH concentration in early postglomerular blood before it reaches the peritubular capillary network. We speculate that PAH and similar substances secreted by the pars recta are short-circuited by rapid extraction from early postglomerular blood, reducing their delivery to the mid-proximal convoluted tubule. Such circumstances must be considered in any analysis of organic compound secretion by the in vivo proximal tubule.
Luminal buffer transport in rat cortical tubule: relationship to potassium metabolism
Authors: Karlmark B. , Jaeger P. , Giebisch G.
Published: December 2017

Free-flow micropuncture studies were performed on superficial rat tubules and titratable acid (TA), sodium and potassium concentrations, and tubular pH were measured in control, acutely K-loaded, and chronically K-depleted animals. The proximal tubule is a key site of TA formation. Under control conditions, significant amounts of TA were lost along the loop of Henle. TA delivery (in pmol X min-1) to the late proximal tubule (LP) was 23.66 +/- 2.38 (mean +/- SE), that to the early distal tubule (ED) was 17.24 +/- 1.73, and little further loss occurred along more distally located nephron sites. In acute hyperkalemia, urinary TA excretion (in mumol X min-1) was lower than under control conditions (0.56 +/- 0.04 vs. 1.01 +/- 0.07); TA delivery to the LP (18.50 +/- 1.93) was slightly reduced compared with the controls (a change not reaching statistical significance). TA delivery to the ED was also reduced (11.54 +/- 1.04); significant amounts of TA were lost along the loop of Henle and a significant further loss occurred along the distal tubule since TA delivery to the late distal tubule (LD) was only 7.41 +/- 0.83. As luminal pH along both proximal and distal tubules in K-loaded rats was indistinguishable from that of control rats, a major factor responsible for decreased distal TA formation in K-loaded animals was diminished buffer delivery. In chronic potassium depletion urinary TA excretion was also lowered (0.30 +/- 0.06); only a moderate part of this effect was due to increased pH along the nephron. Increased buffer reabsorption along the proximal tubule (TA delivery to LP was 14.32 +/- 2.01) contributed mainly to the reduced rate of titratable acid excretion.
Mode of inhibition of active chloride transport in the frog cornea by furosemide
Authors: Patarca R. , Candia O. A. , Reinach P. S.
Published: December 2017

The mechanism of inhibition of active Cl- secretion by 1 mM furosemide and 0.1 mM bumetanide was characterized in the isolated frog corneal epithelium. Transepithelial and transmembrane cell electrical parameters as well as transmembrane Cl- electrochemical potential difference were measured with conventional glass microelectrodes and Cl- selective microelectrodes. Furosemide caused the potential difference across the apical membrane to hyperpolarize by 20 mV while the transepithelial potential difference declined by 13 mV. The apical-to-basolateral membrane resistance ratio increased 3-4 times after furosemide or bumetanide addition. Preincubation with furosemide prevented a 30-mV depolarization of the apical membrane potential difference normally observed when Cl- was removed from the tear side bathing solution. In control conditions, intracellular Cl- activity was above equilibrium. Bumetanide further increased the Cl- electrochemical gradient between the cell compartment and the bathing solutions even though intracellular Cl- activity fell from 18 to 12 mM. In contrast, perfusion with Cl- -free Ringer in the stromal side bathing solution decreased the Cl- electrochemical gradient across the apical membrane to zero, indicating an equilibrium distribution. Adenosine, which selectively increases Cl- permeability of the apical membrane, also decreased the Cl- electrochemical gradient across the apical membrane. These results suggest that the diuretics inhibit active Cl- transport primarily by decreasing the Cl- permeability of the apical membrane.
Canine renal vascular response to hyperoncotic dextran in kidneys with or without glomerular filtration
Authors: Gotshall R. W.
Published: December 2017

The effect of intrarenal arterial infusion of hyperoncotic dextran on renal hemodynamics and excretion was studied in anesthetized dogs. To examine the role of glomerular filtration and tubular flow in the hemodynamic response, several kidney models were employed. Nonfiltering kidneys (NFK) were produced by combined ischemia and ureteral obstruction (UO). Additionally, kidneys with only UO and a lack of filtration as well as kidneys with only ischemia and glomerular filtration were studied. Renal blood flow in normal kidneys was increased by hyperoncotic dextran from 357 +/- 47 to 486 +/- 65 ml X min-1 X 100 g-1, with a corresponding decrease in renal vascular resistance. Ischemic kidneys responded likewise to the dextran infusion, increasing renal blood flow from 261 +/- 31 to 339 +/- 29 ml X min-1 X 100 g-1. Glomerular filtration rate was reduced by the dextran infusion from 80.1 +/- 7.9 to 60.7 +/- 6.6 in normal kidneys and from 31.8 +/- 9.6 to 20.2 +/- 5.8 ml X min-1 X 100 g-1 in ischemic kidneys. Urine flow and sodium excretion were also reduced in these kidneys. In contrast, both NFK and UO, which lacked filtration and tubular flow, did not vasodilate in response to dextran. Renal blood flow remained unchanged from control values (NFK: 146 +/- 6, UO: 111 +/- 22 ml X min-1 X 100 g-1) in these kidneys. These experiments show that the renal vascular response to hyperoncotic dextran is not due to a change in blood volume or viscosity nor to a direct pharmacologic action of dextran. The most likely explanation is that hyperoncotic dextran alters tubuloglomerular feedback control of renal vascular resistance by decreasing filtration and altering tubular flow and/or composition. However, the involvement of another intrarenal vasodilatory system cannot be discounted.
Nephron sites of action of nicotinamide on phosphate reabsorption
Authors: Haas J. A. , Berndt T. J. , Haramati A. , Knox F. G.
Published: December 2017

The administration of nicotinamide results in urinary phosphate excretions similar to those obtained with pharmacologic doses of parathyroid hormone (PTH). Free-flow micropuncture was performed to localize the nephron site(s) of inhibition of phosphate reabsorption by nicotinamide or PTH in thyroparathyroidectomized (TPTX) rats stabilized on a normal or low phosphate diet. In rats fed a normal phosphate diet phosphaturia was observed following either nicotinamide or PTH treatment. Nicotinamide inhibited phosphate reabsorption in the loop of Henle (pars recta) but not in the accessible proximal tubule. PTH inhibited phosphate reabsorption in both the accessible proximal tubule and the pars recta. In phosphate deprivation, the phosphaturic response to either nicotinamide or PTH was blunted. Although phosphate reabsorption was markedly inhibited in the accessible proximal tubule with both nicotinamide and PTH, subsequent reabsorption in the loop of Henle and distal tubule blunted the phosphaturia. We conclude that nicotinamide primarily inhibits phosphate reabsorption by the pars recta in rats fed a normal phosphate diet, whereas it inhibits phosphate reabsorption by the proximal convoluted tubule in rats fed a low phosphate diet. Furthermore, avid reabsorption of phosphate in the pars recta accounts for the resistance to the phosphaturic effect of nicotinamide or PTH seen in rats fed a low phosphate diet.
Evidence of corticosteroid action along the nephron
Authors: Marver D.
Published: December 2017

The kidney contains three classes of corticosteroid-binding proteins receptors. They include a mineralocorticoid-specific (Type I), a glucocorticoid-specific (Type II), and a corticosterone-specific (Type III) site. The Type I and Type III sites roughly parallel each other along the nephron, with maximal binding occurring in the late distal convoluted or connecting segment and the cortical and medullary collecting ducts. Type II sites occur throughout the nephron, with maximal concentrations appearing in the proximal tubule and the late distal convoluted-cortical collecting duct region. The function of the Type I sites in the connecting segment is unclear since chronic mineralocorticoid therapy does not influence the potential difference in this segment as it does in the cortical collecting tubule. Furthermore, the specific role of Type II versus Type III sites in the distal nephron is unknown. Finally, the possible influence of sodium on both latent and steroid-induced renal cortical and medullary Na-K-ATPase is discussed.
Determinants of axial osmotic gradients in the differentiating countercurrent system
Authors: Horster M. F. , Gilg A. , Lory P.
Published: December 2017

The renal medullary countercurrent system differentiates into its final segmental nephron function and geometry during perinatal development. The influence of these changes on the medullary longitudinal osmotic gradient cannot be evaluated by experimental studies. Therefore, a computation analysis using a differential equation model of the renal countercurrent system was applied to quantitate the effect of medullary architecture and solute transport on the concentration profiles for salt and urea in tubules (loop of Henle and collecting duct) and in the central core along the entire medulla during ontogeny. The results indicate that both the changing distribution of loop segments within the medulla and the increase in active salt transport of the individual thick ascending loop determine the magnitude and slope of the axial medullary solute gradients.
Recovery of proximal tubular function from ischemic injury
Authors: Johnston P. A. , Rennke H. , Levinsky N. G.
Published: December 2017

Fluid (sodium) reabsorption, total glucose efflux, and reabsorption of angiotensin II and insulin from the proximal convoluted tubule were studied in rats by in vivo microperfusion. After 35 min of total renal artery occlusion, function was assessed at two intervals, 0-1 h (early recovery, ER) and 2-4 h (late recovery, LR). Light and electron microscopic evaluation showed 60-75% loss of proximal convoluted tubule brush border membrane in ER and nearly complete restoration of brush border in LR. No other structural abnormalities were evident. Renal blood flow was unchanged from control during both ER and LR. During ER, fluid reabsorption was reduced to 29.8 +/- 5.2%, and total glucose efflux, at normal tubule loads, to 73.9 +/- 5.5% of control. However, angiotensin II and insulin reabsorption were unchanged. In LR, fluid reabsorption remained significantly reduced at 54.3 +/- 8.1% of control. Total glucose efflux from the proximal tubule was normal in LR at glucose loads of up to 400 pmol X min-1, but was significantly reduced at higher loads. Passive glucose efflux, measured in the presence of 10(-4)M phloridzin, was not altered by ischemia. Brief ischemia results in significant alterations in proximal tubular reabsorption of sodium and glucose, which correlate with a substantial loss of brush border during ER. However, despite restoration of cell morphology to normal in LR, transport defects for both sodium and glucose persist.
Mechanisms of escape from sodium retention during angiotensin II hypertension
Authors: Hall J. E. , Granger J. P. , Hester R. L. , Coleman T. G. , Smith M. J. , Cross R. B.
Published: December 2017

This study examined the role of increased renal arterial pressure (RAP) in renal escape from the chronic Na-retaining effects of angiotensin II (ANG II). When RAP was allowed to increase during ANG II infusion (5 ng X kg-1 X min-1), urinary Na excretion (UNaV) decreased transiently on the first day but there was no significant change in Na iothalamate space or cumulative Na balance when ANG II infusion was continued for 6 days. Mean arterial pressure (MAP) rose from 100 +/- 3 to 132 +/- 2 mmHg after 3 days and remained near that level for the next 5 days of ANG II infusion. When RAP was prevented from rising with a servo-controlled aortic occluder, UNaV remained below control even after 6 days of ANG II infusion, cumulative Na balance increased by 210 +/- 37 meq, and Na iothalamate space rose by 1,158 +/- 244 ml. MAP did not plateau when RAP was servo-controlled during ANG II infusion but continued to rise and after 6 days averaged 157 +/- 3 mmHg. In three of the eight dogs in which RAP was servo-controlled during ANG II infusion, Na and water retention became so severe that MAP increased to 165-180 mmHg and pulmonary edema developed within 4-6 days. These data suggest that a rise in RAP is essential in allowing the kidneys to escape from the chronic Na-retaining actions of ANG II and in attaining Na balance and a stable level of MAP without severe volume expansion.
Measurement of inhibitors of calcium phosphate precipitation in plasma ultrafiltrate
Authors: Rufenacht H. S. , Fleisch H.
Published: December 2017

Two methods are described to measure quantitatively the inhibitory activity of calcium phosphate precipitation in undiluted plasma ultrafiltrates. The first, called the "seed test," is based on the determination of the amount of apatite needed to induce the precipitation of calcium phosphate from the ultrafiltrate that previously had been brought to a constant [Ca X Pi] supersaturation. The second, called the "supersaturation test," is based on the determination of the minimum [Ca X Pi] product necessary to induce the precipitation of calcium phosphate, care being taken to eliminate the influence of chelators. With both techniques pyrophosphate was found to be the most effective inhibitor, magnesium and citrate being less active. At the physiological concentrations present in plasma ultrafiltrate, magnesium represented the greatest part of the activity in the seed test, while pyrophosphate was the most important in the supersaturation test. However, the three known inhibitors represented only part of the total inhibitory activity. In a pilot study, patients with renal failure showed an increase in inhibitory activity both in the known and unknown fractions.
Na+ gradient-dependent Pi uptake in basolateral membrane vesicles from dog kidney
Authors: Schwab S. J. , Klahr S. , Hammerman M. R.
Published: December 2017

To ascertain whether Na+ gradient-stimulated 32Pi uptake was demonstrable in renal basolateral membrane vesicles, we measured 32Pi uptake in basolateral membrane suspensions isolated from canine renal cortex and compared solute uptake in basolateral suspensions with that measured in brush border suspensions. Measurements revealed Na+ gradient-dependent 32Pi transport in basolateral preparations. D-[3H] Glucose uptakes in basolateral suspensions were not stimulated by the Na+ gradient in contrast to findings in brush border suspensions. Na+ gradient-dependent 32Pi transport in basolateral suspensions was electrogenic in contrast to that measured in brush border preparations. Unlike 32Pi uptake in brush border preparations, Na+ gradient-dependent 32Pi uptake in basolateral suspensions did not increase as extravesicular pH was increased from 6.5 to 7.5. Na+ gradient-dependent 32Pi uptake in basolateral membranes showed saturation over the range of [Pi] from 5 to 100 microM (apparent Km, 14 +/- 2 microM; apparent Vmax, 34 +/- 2 pmol Pi X mg protein-1 X 30s-1). Our findings are compatible with the presence of an electrogenic Na+-Pi cotransporter in the canine proximal tubular basolateral membrane.
Release of active and inactive renin from hog renal cortical slices in vitro
Authors: Okamura T. , Inagami T.
Published: December 2017

Both inactive and active renin were released from renal cortical slices of the hog. Isoproterenol, prostaglandin E1, and dibutyryl cAMP stimulated the release of both inactive and active renin. Renal kallikrein caused selective stimulation of the release of active renin and suppressed the release of inactive renin. Bradykinin and kallidin did not stimulate renin release. The effect of kallikrein was abolished by aprotinin but not by indomethacin. These observations indicate that the effect of kallikrein is not mediated via kinin formation or prostaglandin generation. The data suggest that there may be at least two types of mechanism for renin release from hog kidney. One is of the nonselective type by which both active and inactive renin are released, as in the case of beta-adrenergic or prostaglandin stimulation. The other is a selective mechanism by which only active renin is preferentially released, as in the case of urinary or renal kallikrein stimulation.
Effects of sodium intake on steady-state potassium excretion
Authors: Young D. B. , Jackson T. E. , Tipayamontri U. , Scott R. C.
Published: December 2017

The effects of changes in sodium intake on the steady-state relationship between plasma potassium concentration and potassium excretion were studied in 15 chronically adrenalectomized dogs. Throughout the experiments the dogs received aldosterone at a rate of 50 micrograms/day and methylprednisolone at 1 mg/day. The relationship between plasma potassium and steady-state potassium excretion was obtained by changing potassium intake from 10 to 30 to 100 meq/day, each level being maintained for 7-10 days. At the conclusion of each period at a given level of potassium intake, plasma potassium and excretion were measured and plotted, plasma potassium being the independent variable. Such a relationship was obtained while the dogs were on three different levels of sodium intake: 10, 100, and 200 meq/day. The curves from the data obtained at 100 and 200 meq/day sodium intake both were shifted to the left of the curve obtained at 10 meq/day (P less than 0.05), although the 100 and 200 meq/day curves were not different from each other. On the basis of these data one could predict that, at a plasma potassium concentration of 4.0 meq/liter, the animals would excrete potassium at a rate of 17 meq/day on a 10 meq/day sodium intake, 37 meq/day on a 100 meq/day sodium intake, and 47 meq/day on a 200 meq/day sodium intake. Urine flow and electrolyte concentration data are consistent with the hypothesis that the sodium intake effect on potassium excretion was mediated through increases in distal nephron flow rate and decreases in distal nephron potassium concentration.
Effect of long- and short-term antidiuretic hormone availability on internephron heterogeneity in the adult rat
Authors: Trinh-Trang-Tan M. M. , Bouby N. , Doute M. , Bankir L.
Published: December 2017

We have previously shown that certain aspects of internephron heterogeneity are reduced or absent in Brattleboro rats with hereditary diabetes insipidus (DI) lacking ADH and can be restored by long-term ADH administration started before complete kidney maturation. In the present study, the effects of long- and short-term availability of ADH in adulthood were studied in Brattleboro DI rats. Single nephron glomerular filtration rate (SNGFR), glomerular volume (GV), and proximal tubular length (PTL) were measured in superficial and juxtamedullary nephrons using the ferrocyanide and microdissection techniques. ADH administration for 6 wk in adult DI rats (group A) restored normal nephron heterogeneity of SNGFR, GV, and PTL by increasing the filtration and size of deep nephrons. Acute changes in ADH availability induced either by 1-h ADH infusion in DI rats (group C) or by ADH discontinuation for 2 days in treated DI rats (group D) did not significantly change the anatomical parameters and only moderately affected SNGFR compared with the preexisting states (groups B and A, respectively). These results suggest that the influence of ADH on internephron heterogeneity is initiated by an increase in deep nephron SNGFR. Based on recent findings concerning the effects of ADH on the medullary (M) part of the thick ascending limbs (TAL), we suggest that the increase in deep nephron SNGFR after ADH may be due to a change in the tubuloglomerular feedback signal at the macula densa resulting from ADH-induced stimulation of the solute reabsorption in the MTAL. Superficial nephrons would be less sensitive to this change due to their long cortical TAL, which removes the macula densa further from the MTAL and provides additional sites for solute reabsorption.
Renal function in rats chronically exposed to high altitude
Authors: Ou L. C. , Silverstein J. , Edwards B. R.
Published: December 2017

Chronic exposure of rats to a simulated altitude of 18,000 ft (5,500 m) results in severe polycythemia and consequent reduction of the plasma fraction. However, glomerular filtration rate is usually well maintained. This study was conducted to determine whether an increase in effective renal blood flow (ERBF) plays a role in maintaining a normal glomerular filtration rate in the chronically hypoxic rats. Various measurements of renal function were made in conscious trained and chronically catheterized animals. After exposure to high altitude for 30 days, hematocrit ranged from 64 to 77%. Despite this severe reduction in the plasma fraction, however, renal plasma flow decreased by only 25%, primarily owing to an increase in ERBF. The glomerular filtration rate was within the normal range. Since blood pressure remained unchanged, the increase in ERBF must have resulted from renal vasodilation. Acute removal of the hypoxic stimulus did not reverse the increased ERBF, suggesting that the vasodilation may have been of structural origin.
Effects of biguanides on short-circuit current in frog skin
Authors: Saito T. , Yoshida S.
Published: December 2017

The addition of phenformin to the solution bathing the mucosal side of frog skin resulted in a sustained stimulation of short-circuit current accompanied by an increase in open-circuit potential and total conductance of the membrane. The flux of 22Na from the mucosal to the serosal side of the skin was increased by phenformin, whereas no significant effect on the flux from the serosal to the mucosal side was observed. The increases in the short-circuit current and total conductance with phenformin were completely abolished by the addition of 5 X 10(-5) M amiloride, which blocks sodium permeability at the apical surface of the membrane. Thus, the stimulation of active sodium transport in frog skin by phenformin would be due to the increase in the amiloride-sensitive sodium permeability of the membrane. Phenformin may prove to be a useful tool for the study of sodium transport in amphibian epithelia.
Analysis of microvascular water and solute exchanges in the renal medulla
Authors: Pallone T. L. , Morgenthaler T. I. , Deen W. M.
Published: December 2017

A theoretical model has been developed to simulate solute and water transport in the medullary microcirculation of the normal hydropenic rat. The model is formulated in terms of a countercurrent vascular unit consisting of one descending (DVR) and several ascending vasa recta (AVR) extending from the corticomedullary junction to the tip of the papilla. Steady-state mass balances relate gradients in NaCl, urea, and plasma protein concentrations and variations in the flow rates of plasma and red blood cells to permeability properties of the vasa recta and erythrocytes. In contrast to previous models, transmural volume fluxes are assumed to be present in both DVR and AVR. Available micropuncture measurements suggesting net volume removal from DVR within the inner medulla are found to be consistent with NaCl reflection coefficients in DVR between 0.10 and 0.80. The hydraulic permeability in the DVR is estimated to be greater than 0.18 X 10(-6) cm X s-1 X mmHg-1. Based on currently available data, reliable bounds cannot yet be placed on the hydraulic permeability of the AVR. The vascular unit is predicted to accomplish substantial net removal of NaCl and water from the inner medullary interstitium but relatively little removal of urea. Red cells leaving the inner medulla in the AVR are found to be slightly dehydrated. It is calculated that at a given blood flow rate, the lower the initial medullary hematocrit, the more effective the vascular unit is at removing water. Several unresolved issues are discussed, including the role of the capillary plexus that joins DVR with AVR. To the extent that the volume uptake observed in the exposed papilla in structures beyond the DVR occurs in the capillary plexus and not in the AVR, estimated values of AVR hydraulic permeability are reduced, as is predicted overall volume uptake by the vascular unit in the inner medulla.
Increased Vmax for Na+/H+ antiporter activity in proximal tubule brush border vesicles from rabbits with metabolic acidosis
Authors: Tsai C. J. , Ives H. E. , Alpern R. J. , Yee V. J. , Warnock D. G. , Rector F. C.
Published: December 2017

Na+/H+ antiporter activity in renal brush border vesicles from control rabbits and rabbits made acidotic with 3 days of NH4Cl gavage was measured using the acridine orange method. Acidotic rabbits exhibited a significantly higher Vmax for antiporter activity (2.80 +/- 0.45 fluorescence units X s-1 X mg protein-1) compared with controls (1.31 +/- 0.13) but the Km for Na+ was unchanged (23.7 +/- 3.5 for acidotic, 19.1 +/- 3.2 mM for controls). When the Vmax for Na+/H+ antiporter activity was considered in relation to the degree of acidosis achieved in the experimental animals, there was a correlation (r = -0.75) between Vmax and plasma total CO2 concentration. Amiloride (100 microM) inhibited Na+/H+ exchange (Na+ = 90 mM) by 59 +/- 7% in both control and acidotic animals, indicating that the observed stimulation in Na+/H+ antiporter activity was not due to increased electrically coupled cation exchange. These findings suggest that the response of the proximal tubule to chronic metabolic acidosis involves an adaptive increase in the Vmax for Na+/H+ antiporter activity in the brush border membrane that is correlated to the degree of acidosis in the animals.
Renal hydrolysis of absorbed protein: influence of load and lysosomal pH
Authors: Camargo M. J. , Sumpio B. E. , Maack T.
Published: December 2017

The kinetics of intracellular hydrolysis of administered protein and the effect of alkalinization of lysosomal pH on this process were studied in the isolated perfused rat kidney (IPK). Cytochrome c (CYT c) was used as a probe protein, and its hydrolysis was determined by measuring the efflux of radioactivity from IPK preloaded in vivo with [14CH3]CYT c and various doses of unlabeled CYT c. The nature of radioactivity absorbed by the kidney and released to the perfusate was analyzed by Sephadex chromatography. Administered CYT c is absorbed and hydrolyzed by the kidney, and the resulting amino acids are returned to the perfusate. At low uptake rates, the half time of hydrolysis of absorbed CYT c is about 20 min. The disposal of absorbed CYT c is a saturable function of its concentration in kidney with a Vmax = 0.60 mg CYT c X h-1 X g kidney-1 and an apparent Km = 0.55 mg CYT c/g kidney. To alkalinize the lysosomal pH, IPK were perfused in the presence of NH4Cl (10 mM) or chloroquine (0.1 mM). These lysosomotropic weak bases almost completely inhibit in a reversible manner the hydrolysis of absorbed CYT c. The results demonstrate that renal catabolism of absorbed protein is a saturable process of high capacity compared with the normal filtered loads of protein. The data are consistent with the view that normal lysosomal function is required for an adequate disposal of absorbed proteins in the kidney. It is postulated that abnormal deposition of protein absorption droplets within renal tubular cells may result from high absorbed loads and/or a deficient acidification of lysosomes.