bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of acute potassium load on reabsorption in Henle's loop in the rat
Authors: Sufit C. R. , Jamison R. L.
Published: December 2017

Rats fed a low potassium diet were studied before and after KCl infusion to determine whether potassium recycling in the renal medulla accelerates potassium excretion by increasing delivery of sodium, water, and potassium to the distal tubule. Fluid samples were obtained from the end-proximal and beginning-distal tubule before and at the same sites after KCl loading by re-collection micropuncture and were compared with samples obtained from similarly fed control animals not infused with KCl. Potassium excretion increased in the KCl group from 3 to 48% but remained low in the controls. Fractional sodium and water delivery to end-proximal and beginning-distal tubule increased with time equally in both groups. Potassium reabsorption in Henle's loop fell from 75 to 58% (P less than 0.005) after KCl infusion but not significantly in the controls (from 77 to 75%). Fractional potassium delivery to the distal tubule increased from 12 to 26% (P less than 0.005) in the KCl group, which could account for over half the potassium excreted. The increase in controls from 12 to 17% was significantly less (P less than 0.02). These findings suggest that potassium recycling reduces potassium reabsorption in Henle's loop, enabling the loop to participate with the distal and collecting tubule in accelerating urinary excretion of an acute potassium load.
Abnormalities in glomerular function in rats developing spontaneous hypertension
Authors: Dilley J. R. , Stier C. T. , Arendshorst W. J.
Published: December 2017

Clearance and micropuncture studies were conducted on 6-wk-old spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain and normotensive Wistar-Kyoto rats (WKY) under euvolemic conditions. Mean arterial pressure in SHR was elevated by 18 mmHg and their kidneys were vasoconstricted with reduced blood flow; resistances in preglomerular vessels and efferent arterioles were elevated 2.8 and 2 times, respectively, above WKY values. Whole kidney glomerular filtration rate (GFR) and single nephron glomerular filtration rate (SNGFR), based on fluid collection from either proximal or distal convolutions, were 25-30% lower in SHR. Fractional reabsorptions of fluid load by the proximal convoluted tubule (43%) and by the loop of Henle (52-55%) were similar in both groups. Accordingly, SHR exhibited less fluid delivery from the proximal convolution (8 vs. 12 nl/min) and to the distal convolution (3 vs. 5 nl/min). Glomerular dynamics in hypertensive and normotensive strains were characterized by filtration pressure disequilibrium. Estimated glomerular capillary pressure and mean effective ultrafiltration pressure were similar in SHR and WKY. SHR had a lower glomerular ultrafiltration coefficient than WKY (0.011 vs. 0.016 nl X s-1 X mmHg-1), which, combined with a lower glomerular plasma flow (41 vs. 73 nl/min), quantitatively accounted for the lower SNGFR in 6-wk-old SHR. These findings document important differences in renal function in young SHR compared with WKY that may participate in the development of hypertension.
Glomerulopathy does not increase renal susceptibility to acute ischemic injury
Authors: Zager R. A. , Baltes L. A. , Sharma H. M. , Couser W. G.
Published: December 2017

To determine whether preexistent glomerular injury and the nephrotic syndrome increase renal susceptibility to ischemic renal injury, normal rats and rats with either experimental minimal-change disease (Adriamycin nephropathy) (AN) or membranous nephropathy (passive Heymann nephritis) (PHN) underwent renal functional and histologic studies under either basal conditions or 18 h after bilateral renal artery occlusion (over 30 min). Prior to renal ischemia AN and PHN rats had minimally depressed glomerular filtration rate (GFR), normal (AN) or increased (PHN) renal blood flow (RBF), heavy proteinuria, hypoalbuminemia, decreased urine sodium excretion, extensive glomerular foot process fusion, and intratubular hyalin cast formation. Losses of GFR in response to ischemia were comparable among the three groups of rats (controls, 0.29; AN, 0.28; PHN, 0.25 ml X min-1 X 100 g body wt-1) despite prevailing differences in postischemic hemodynamics. Neither light nor transmission electron microscopy showed any differences in the degree of ischemic renal injury. These results suggest that 1) glomerulopathy and the nephrotic syndrome do not significantly increase renal susceptibility to ischemic renal injury; 2) the syndrome of acute renal failure that occurs in patients with minimal-change glomerulopathy is not due to a marked susceptibility of these kidneys to clinically occult ischemic events; and 3) foot process fusion is probably not a pathophysiologically significant lesion in ischemic acute renal failure, as previously suggested.
Passive and active ion transport by the urinary bladder of a euryhaline flounder
Authors: Demarest J. R. , Machen T. E.
Published: December 2017

The effects of voltage clamping on the flux ratios and unidirectional and net fluxes of Na and Cl were used to gain insight into the mechanisms of active and passive ion transport across urinary bladders isolated from seawater-(SW) and freshwater-acclimated (FW) flounder, Platichthys stellatus. Although the transepithelial conductance (Gt = 2.77 mS X cm-2) of FW bladders was much greater than that of SW bladders (Gt = 0.40 mS X cm-2), the current-voltage relationships of both SW and FW bladders were markedly nonlinear. Under short-circuit conditions there was a large difference in the serosal-to-mucosal Na flux (JNasm) between SW (0.10 mueq X cm-2 X h-1) and FW (1.71 mueq X cm-2 X h-1) bladders, but their mannitol permeabilities were identical. The results indicate that 1) the paracellular pathway of both SW and FW bladders is Cl selective and Cl movements through the shunt account for a maximum of 90% of Gt in SW bladders and 19% in FW bladders; 2) the larger Gt of FW bladders is due to greater conductance of the apical cell membrane; 3) the majority of the passive ion movement across these epithelia proceeds through nonconductive, presumably transcellular, pathways; and 4) active transport of Na and Cl occurs by neutral coupling to each other and to other unidentified ions.
Assessment of mineralocorticoid activity in the rabbit colon
Authors: Marver D.
Published: December 2017

Analyses of [3H]corticosteroid binding sites in distal colon indicated high-affinity binding sites or receptors for both [3H]aldosterone (Type I, Kd = 6.5 X 10(-9) M) and [3H]dexamethasone (Type II, Kd = 5.5 X 10(-8) M). The relative affinity of dexamethasone (D) was 1/20 that of aldosterone (A) for Type I sites and the affinity of A for Type II sites was 1/50 that of D at 37 degrees C. Citrate synthase (CS) activity was assayed and found to be reduced in enterocytes harvested from adrenalectomized (ADX) vs. normal colon segments (0.24 vs. 0.44 U/mg protein, P less than 0.025). Aldosterone (10 micrograms/kg body wt) increased CS at 2 h to a level intermediate between normal and ADX animals and thus not significantly different from either group, but was significantly increased over ADX + D values. Transmural potential difference was increased by 10(-8) M A but not by 10(-8) M D. Since both steroids enhanced short-circuit current at this concentration, the dichotomy of the glucocorticoid vs. mineralocorticoid results can be best explained by the pronounced effect of D on resistance (R) across the tissue (R at 4 h + D was 50% that of paired controls). These findings would suggest that the rabbit distal colon is a target segment for both mineralocorticoids and glucocorticoids. Furthermore, as in the kidney, the two steroids may play coordinated but, perhaps in some way, unique roles in the regulation of transport.
Placental transport of calcium and phosphorus is not regulated by vitamin D
Authors: Brommage R. , DeLuca H. F.
Published: December 2017

The role of 1,25-dihydroxyvitamin D3 in regulating the maternal-to-fetal transfer of calcium and phosphorus across the placenta was examined by measuring maternal and fetal plasma levels of these elements in vitamin D-replete and -deficient rats. Pregnant rats in their 20th day of gestation and their fetuses were studied. Two diets with different calcium and phosphorus contents were used to produce either hypocalcemia or hypophosphatemia in the vitamin D-deficient rats. Calcium and phosphorus levels in fetal plasma were always higher than maternal values, and in vitamin D deficiency a twofold gradient of calcium and a fivefold gradient of phosphorus concentrations across the placenta were observed. Since protein levels in fetal plasma were approximately fivefold lower than maternal values, protein binding does not account for the higher fetal than maternal concentrations of plasma calcium. These results, together with previous data showing normal calcium content of vitamin D-deficient fetuses, indicate that 1,25-dihydroxyvitamin D3 and other vitamin D3 metabolites are not involved in the active transport of calcium and phosphorus across the placenta in the rat.
Calcium restriction and parathyroid hormone enhance renal compensatory growth
Authors: Jobin J. , Taylor C. M. , Caverzasio J. , Bonjour J. P.
Published: December 2017

Calcium has been shown to control the proliferation of various cells in vitro and in vivo. Despite this information it is not known whether the Ca status or Ca-regulating hormones could modulate the degree of compensatory growth of the remaining kidney after renal mass reduction. In the present work the influence of dietary Ca, parathyroid hormone (PTH), and calcitonin (CT) on renal compensatory growth ( RCG ) was studied in unilaterally nephrectomized (UNI-NX) rats. UNI-NX rats were pair-fed diets with high (1.1%, HCa) or low (0.1% LCa) Ca content for 3, 8, and 15 days. After UNI-NX the wet weight of the remaining kidney increased much more in rats fed LCa than HCa. Values of dry weight, total protein, and DNA content were also significantly higher in the remaining kidney removed from rats fed LCa than from those fed HCa. LCa did not display such effects in sham-operated rats with intact renal mass. The amount of dietary Ca did not influence the progressive rise in glomerular filtration rate (clearance of inulin) of the remaining kidney as assessed 3, 8, and 15 days after UNI-NX. In UNI-NX rats fed LCa chronic administration of CT in doses that induced hypocalcemia did not inhibit the enhanced RCG induced by LCa. In UNI-NX rats fed HCa chronic administration of PTH mimicked the effect of LCa. In conclusion, dietary Ca restriction can markedly enhance the compensatory but not the normal growth of the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
Attenuated pressure natriuresis in the early phases of two-kidney Goldblatt hypertension
Authors: Rostand S. G. , Kirk K. A.
Published: December 2017

We studied the effect of changing perfusion pressure on the excretory function of isolated perfused nonclipped kidneys from the two-kidney Goldblatt hypertensive rat ( GHR ). Kidneys were studied from newly hypertensive rats about 8 days after contralateral renal artery clipping [blood pressure (BP) 138 +/- 4.3 mmHg] and before onset of hypertension 3 days following surgery (BP 111 +/- 1.9 mmHg). In addition, nonclipped kidneys from adrenalectomized Goldblatt rats were also examined approximately 9 days following surgery (BP 114 +/- 4.7 mmHg). Kidneys from sham-operated rats served as controls. We noted no differences in GFR in kidneys from newly hypertensive rats and sham controls above a perfusion pressure of 120 mmHg. In response to increasing perfusing pressure, perfusate flow and fractional sodium excretion were significantly lower in newly hypertensive rats than in sham-operated controls. No differences in glomerular filtration rate, perfusate flow, or sodium excretion were noted in kidneys from sham-operated rats or Goldblatt rats 3 days following surgery. After clipping, adrenalectomized (ADX) Goldblatt rats had less of a rise in blood pressure than did rats with intact adrenal glands. No attenuation of natriuresis was noted in the ADX-clipped group in response to increasing perfusion pressure. Isolated perfused kidneys from ADX rats had greater sodium excretion at all levels of pressure than kidneys from rats with intact adrenal glands. Deoxycorticosterone acetate replacement returned sodium excretion to that approaching intact rats. We conclude that nonclipped kidneys of newly hypertensive Goldblatt rats exhibit blunted pressure natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro
Authors: Perrone R. D. , Jenks S. L.
Published: December 2017

Basal Na absorption in the rat colon is coupled to that of Cl in an electroneutral fashion. We previously determined that aldosterone or dexamethasone induces amiloride-sensitive mucosal-to-serosal Na flux approximately equal to the amiloride-sensitive short-circuit current in rat distal colon in vitro. However, the effect of these steroids on coupled Na-Cl absorption was not examined. For this purpose, we determined the unidirectional flux of Na and Cl in voltage-clamped distal colon segments from rats treated with aldosterone or dexamethasone. Amiloride was used as a probe for conductive Na absorption, and acetazolamide and Cl-free solutions were used as probes for coupled Na-Cl absorption. Our results indicate that the nature of colonic Na absorption is markedly changed after treatment with these steroids. In contrast to findings in the untreated rat, colonic Na absorption after treatment with aldosterone or dexamethasone was largely independent of the presence of Cl. Net Cl absorption and acetazolamide sensitivity were both greatly diminished. Thus, aldosterone and dexamethasone have multiple effects on Na transport in rat distal colon. In addition to the stimulation of conductive Na absorption by aldosterone, an effect well described in other epithelia, there is marked suppression of coupled Na-Cl absorption. Dexamethasone was less effective in suppressing Cl absorption but equally effective in stimulating conductive Na absorption. These steroid effects were greater in the terminal 1-2 cm of the rat colon.
Effects of isoproterenol on potassium secretion by the cortical collecting tubule
Authors: Kimmel P. L. , Goldfarb S.
Published: December 2017

These studies tested the effects of isoproterenol on potassium secretion in the isolated perfused cortical collecting tubule. Isoproterenol, 10(-6) M (n = 6) and 10(-4) M (n = 2), added to bathing solution produced a significant fall in potassium secretion [13.5 +/- 1.2 to 8.0 +/- 0.9 peq X mm-1 X min-1 (P less than 0.01)] and in transepithelial voltage (P less than 0.01) compared with time controls (n = 9). Pretreatment with propranolol abolished this effect (n = 4). Addition of propranolol alone to the bath caused no significant change in potassium secretion (n = 8). 8-[p-Chlorophenylthio]cAMP (10(-4) M, isotonic perfusate) added to the bath produced a significant fall in potassium secretion [11.5 +/- 1.7 to 7.2 +/- 1.3 peq X mm-1 X min-1, n = 7 (P less than 0.01)]. Arginine vasopressin (25 microU/ml), which also stimulates adenylate cyclase activity in this segment, had no significant effect on potassium secretion (n = 10). When chloride was replaced by methyl sulfate in all solutions (n = 6), there was a significant attenuation in the fall in potassium secretion in experiments with 10(-6) M isoproterenol compared with experiments with chloride-containing bath solutions (P less than 0.05). These data suggest that isoproterenol has a specific action of reducing potassium secretion in the cortical collecting tubule either through alternating chloride transport per se or through some other effect dependent on the presence of chloride (e.g., hydrogen ion secretion). Also, this effect is probably mediated by cAMP-dependent events. The lack of effect of vasopressin on potassium secretion suggests that separate cells or cellular pools of cAMP are involved in hormonal stimulation by isoproterenol and vasopressin in this nephron segment.
Influence of vasopressin on renal hemodynamics in conscious Brattleboro rats
Authors: Gellai M. , Silverstein J. H. , Hwang J. C. , LaRochelle F. T. , Valtin H.
Published: December 2017

The influence of vasopressin on renal hemodynamics was assessed by treating conscious Brattleboro homozygotes (DI rats) both acutely and chronically with physiologic doses of vasopressin. Intravenous infusions of vasopressin for 1 h, resulting in plasma vasopressin concentrations of less than 1.25, 2.3, and 8.0 pg/ml, respectively, failed to change glomerular filtration rate (GFR) or effective renal blood flow (ERBF) significantly, nor were there significant changes during 5 h of infusion. Body weight was not altered during these infusions. When synthetic vasopressin was given by osmotic minipumps for 10 days, with the rats gaining weight and thus changing the volume of their body fluids, GFR and ERBF increased significantly, by approximately 45 and 55%, respectively. Acute administration of volume alone, as well as acute vasopressin plus acute administration of volume, did not alter GFR or ERBF significantly. The data are compatible with the view that vasopressin, in physiologic plasma concentrations, exerts an influence on renal hemodynamics, that may be mediated through the long-term alteration of body fluid volumes. Alternatively or additionally, prolonged exposure of DI rats to vasopressin may increase their renal hemodynamics through tubuloglomerular feedback.
Proximal tubule site of inhibition of phosphate reabsorption by calcitonin
Authors: Berndt T. J. , Knox F. G.
Published: December 2017

The present study was performed to evaluate the nephron site of inhibition by calcitonin of phosphate reabsorption in the thyroparathyroidectomized rat. Pharmacologic doses of salmon calcitonin markedly inhibited fluid and phosphate reabsorption by the superficial proximal tubule. However, continued phosphate reabsorption between the superficial late proximal and early distal tubule, as well as along the distal tubule, blunted the phosphaturic effect of calcitonin. We conclude that the phosphaturic effect of a pharmacologic dose of salmon calcitonin is primarily due to an inhibition of fluid and phosphate reabsorption by the proximal convoluted tubule.
Rate of formation and composition of absorbate from proximal nephron segments
Authors: Barfuss D. W. , Schafer J. A.
Published: December 2017

Proximal convoluted (PCT) and proximal straight (PST) tubules from rabbit kidney were isolated and subsequently perfused under light mineral oil so that absorbate could be collected. Volume absorption rates in both segments were comparable to those observed during conventional perfusion in aqueous bathing solution. However, volume absorption in the PCT was significantly decreased by reduction or elimination of preferentially absorbed solutes from the perfusate. As previously observed in the PST, glucose was actively absorbed by the PCT against concentration gradients of up to 26 mM. In contrast, the Cl- concentration of the PCT absorbate was less than that in the lumen, presumably due to preferential HCO3- absorption. In the PST, the Na+ concentration of the absorbate exceeded that in the lumen and, given the negligible measured transepithelial voltage, active transepithelial Na+ transport was demonstrated. In contrast, in the PCT, when preferentially absorbed solutes were present in the perfusate at normal concentrations, the absorbate Na+ concentration was significantly less than that in the lumen. This low absorbate Na+ concentration may be due to the dilutional effect of more rapid fluid absorption in the presence of the preferentially absorbed solutes. When the concentrations of these solutes in the perfusate were reduced or eliminated, the absorbate Na+ concentration was not significantly different from that in the lumen.
Quantitation of [3H]ouabain binding and turnover of Na-K-ATPase along the rabbit nephron
Authors: El Mernissi G. , Doucet A.
Published: December 2017

To determine the number of Na-K-ATPase units and the enzyme's turnover rate along the rabbit nephron, the specific binding of [3H]ouabain and the Na-K-ATPase activity were measured in single nephron segments microdissected from collagenase-treated kidneys. The highest density of Na-K-ATPase (20-30 fmol X mm-1) was found in the distal convoluted tubule and the medullary thick ascending limb. Binding was intermediate (10 fmol X mm-1) in the proximal convoluted tubule and connecting tubule, and it was lowest (2-7 fmol X mm-1) in the pars recta, the cortical thick ascending limb, and the collecting tubule. In the medullary thick ascending limb, Scatchard analysis of the specific [3H]ouabain binding indicated a dissociation constant of 1.8 microM. The pump activity was proportional to the number of catalytic units, indicating that the maximal turnover rate of Na-K-ATPase (2,000 ATP molecules per minute per ouabain binding site) was similar in the various segments of the nephron. The method developed for quantitating [3H]ouabain binding is technically simple enough to permit simultaneous measurement of the enzyme in large numbers of tubules and sufficiently sensitive to determine the number of Na-K-ATPase units in each region of the nephron.
Effects of acidosis and carbonic anhydrase inhibition in the elasmobranch rectal gland
Authors: Swenson E. R. , Maren T. H.
Published: December 2017

We studied the effects of acidosis and carbonic anhydrase inhibition on rectal gland fluid secretion. In the anesthetized dogfish shark, Squalus acanthias, volume expanded by a constant infusion of Ringer solution, fluid formation was halved by severe systemic metabolic and respiratory acidosis (pH approximately 7.10) and carbonic anhydrase inhibition. Mild respiratory acidosis (pH approximately 7.6) equivalent to the measured systemic pH during carbonic anhydrase inhibition was without effect. Inhibition of rectal gland enzyme produced severe glandular acidosis, which is indicated by an increase in gland fluid PCO2 (from 7 to 26 mmHg) and HCO3- (from 1.2 to 2.4 mM) and a decrease in pH (from 6.7 to 6.4). Gland tissue total CO2 dropped from 18 to 11 mmol/kg. These changes occurred despite nearly 50% reduction in fluid formation, O2 consumption, and CO2 output. We propose that carbonic anhydrase facilitates CO2 transfer from sites of metabolism to capillary blood by its conversion to HCO3-. This maintains a tolerable intracellular acid-base milieu during stimulated fluid secretion.
Vasopressin and urine flow rate responses to stress in conscious dogs
Authors: Koepke J. P. , Light K. C. , Obrist P. A. , Morris M.
Published: December 2017

Behavioral stress increases arterial pressure while decreasing urine flow rate; the urine flow rate response can be abolished by surgical renal denervation. In this study, the effects of infusion of alpha-adrenoceptor antagonists (intravenous phenoxybenzamine or prazosin) on the antidiuretic and plasma vasopressin responses to stress were examined. Without alpha-adrenoceptor blockade, 20 min of stress increased arterial pressure and decreased urine flow rate, but no change in urine osmolality or plasma vasopressin concentration occurred. Arterial pressure and urine flow rate returned to base-line level during a 20-min recovery period. With alpha-adrenoceptor blockade, which prevented the arterial pressure response to stress, urine flow rate still decreased during stress, but urine osmolality and plasma vasopressin concentration increased. The decrease in urine flow rate and increase in urine osmolality and plasma vasopressin concentration persisted into the first 20-min recovery period but returned to base-line level during a second 20-min recovery period. We conclude that the antidiuretic response to behavioral stress in conscious dogs with saline infusion alone is not mediated via a change in vasopressin release. In contrast, the antidiuretic response to behavioral stress with alpha-adrenoceptor antagonist infusion may be mediated via an increased release of vasopressin.
Antagonistic effect of theophylline on the adenosine-induced decreased in renin release
Authors: Spielman W. S.
Published: December 2017

The action of theophylline on the adenosine-induced decrease in renin release was studied in anesthetized dogs. Adenosine inhibited renin release, decreased GFR and fractional sodium excretion, and decreased the concentration of angiotensin II in the renal lymph. Theophylline (5 mumol/min intrarenally) had no significant effect on GFR or RBF yet produced a significant increase in the release of renin and the fractional excretion of sodium. The intrarenal infusion of adenosine (3 X 10(-7) mol/min) during theophylline infusion produced no effect on GFR or RBF, but fractional sodium excretion and renin release were significantly decreased. Adenosine was infused at a lower dose (3 X 10(-8) mol/min) during theophylline (5 X 10(-6) mol/min) infusion in a second group of dogs. With the exception of fractional sodium excretion, all effects of adenosine were effectively antagonized by theophylline. Theophylline at 5 X 10(-6) mol/min, which stimulates renin release and effectively antagonizes the renal effects of adenosine, had no detectable effect on cAMP measured in renal cortex. Furthermore, no change in cortical cAMP was observed until theophylline was increased 50-fold over the dose effective in antagonizing adenosine. These findings demonstrate that theophylline, at concentrations having no effect on cortical cAMP, antagonizes the effect of adenosine on renin release. The results are also consistent with the view that theophylline stimulates renin release by a mechanism other than its action on cAMP.
Microelectrode assessment of chloride-conductive properties of cortical collecting duct
Authors: Sansom S. C. , Weinman E. J. , O'Neil R. G.
Published: December 2017

The chloride-conductive properties of the isolated rabbit cortical collecting duct were assessed with microelectrode techniques. The transepithelial, apical, and basolateral membrane potential differences, Vte, Va, and Vb, respectively, were monitored continuously along with periodic measurements of the transepithelial conductance, Gte, and fractional resistance, fRa (ratio of apical to apical plus basolateral membrane resistance). Active transport was eliminated in all experiments by luminal addition of 50 microM amiloride in HCO3-free solutions. Upon reducing the chloride activity in the bath (gluconate replacement), there was a marked depolarization of Vb and decrease in Gte and fRa, demonstrating a major dependence of the basolateral membrane conductance on the bath chloride activity. However, a significant K+ conductance at that barrier was also apparent since raising the bath K+ concentration caused an increase in Gte and fRa and depolarization of Vb. Lowering the chloride activity of the perfusate caused a consistent decrease of Gte but not of fRa, effects consistent with a high C1- conductance of the tight junction and little, if any, apical membrane C1- conductance. By use of the C1- -dependent conductances, the C1- permeabilities at equilibrium were estimated to be near 1.0 X 10(-5) cm X s-1 for the tight junction, PtiC1, and 5 X 10(-5) cm X s-1 for the basolateral cell membrane, PbC1. It is concluded that the paracellular pathway provides a major route for transepithelial C1- transport. Furthermore, since the isotopically measured C1- permeability is severalfold greater than PtiC1, a significant transcellular flux of C1- must exist, implicating a neutral exchange mechanism at the apical cell membrane in series with the high basolateral membrane C1- conductance.
Inactivation of atrial natriuretic substance by kallikrein
Authors: Briggs J. P. , Marin-Grez M. , Steipe B. , Schubert G. , Schnermann J.
Published: December 2017

To further characterize the properties of the potent natriuretic and diuretic substance that can be extracted from atrial tissue, we investigated its susceptibility to inactivation by kallikrein and other proteolytic enzymes. Extracts of rat atrial tissue (tissue wet wt 100 mg/ml) were incubated with enzymes under standard conditions and tested by injection into nondiuretic anesthetized rats. One hour of incubation at 37 degrees C with pure porcine pancreatic kallikrein at concentrations of 250 micrograms/ml or greater significantly reduced the activity of atrial natriuretic substance. The reduction in activity was dependent on both enzyme concentration and time of incubation. The kallikrein-catalyzed degradation was completely blocked by aprotinin but was only partially retarded by soybean trypsin inhibitor. Trypsin reduced natriuretic and diuretic activity of extracts at concentrations of 400 micrograms/ml or greater, with nearly complete inactivation at a concentration of 1,000 micrograms/ml. Carboxypeptidase B also caused a concentration-dependent inactivation of the natriuretic material. Last, alpha-chymotrypsin (1,000 micrograms/ml) and elastase (1,000 micrograms/ml) were found to destroy the natriuretic activity. In a separate set of experiments natriuretic activity was observed to be retained by a 1,000 mol wt cutoff membrane. Inactivation of the natriuretic peptide by renal kallikrein is a possible mechanism for in vivo regulation of natriuretic activity.
Sinoaortic baroreceptors and the control of blood volume in the nonhuman primate
Authors: Cornish K. G. , McCulloch T. , Gilmore J. P.
Published: December 2017

The purpose of this study was to determine the role of the aortic and carotid baroreceptors in regulating blood volume in the conscious non-human primate. Eighteen control animals were surgically instrumented to permit the recording of blood pressure, pulse rate, and left atrial pressure. After a urethral catheter was inserted into the bladder, the animals were given an intravenous infusion equal to 20% of the estimated blood volume. Renal function was determined before and after the volume expansion. Nine monkeys received the same infusion after undergoing chronic sinoaortic denervation. The denervated animals responded with a potentiated diuresis and natriuresis. The control animals excreted 24% of the infused volume and 4% of the infused salt while the sinoaortic-denervated animals excreted a volume equal to 113% of that infused and an amount of sodium equal to 46% of that infused. We conclude that high-pressure receptors exert an inhibitory influence on whatever mechanisms are involved in the renal response to acute volume expansion.
Effect of ouabain on K secretion in cortical collecting tubules from adrenalectomized rabbits
Authors: Wingo C. S.
Published: December 2017

Previous studies have shown that Na-K-ATPase activity in the cortical collecting tubule of the rabbit increases significantly with mineralocorticoid stimulation and decreases significantly with adrenalectomy. The present study examined the effects of 10(-4) M ouabain on K secretion in the isolated perfused cortical collecting tubules from normal, adrenalectomized, and mineralocorticoid-stimulated animals. Potassium secretion was similar in the tubules from adrenalectomized (3.42 +/- 0.53 pmol X mm-1 X min-1) and from normal rabbits (3.38 +/- 0.36 pmol X mm-1 X min-1). K secretion was greater (15.1 +/- 3.0 pmol X mm-1 X min-1) in tubules from animals receiving 11-deoxycorticosterone acetate (DOCA). Ouabain inhibition of K secretion was 74% for the adrenalectomized group, 86% for the normal group, and 98% for the DOCA-treated group. The degree of inhibition was statistically equivalent among the three groups and not statistically different from complete inhibition of K secretion. Ouabain had no effect on the lumen-positive transepithelial voltage of the cortical collecting tubules from adrenalectomized rabbits but reduced the lumen-negative voltage in tubules from normal rabbits and reversed the polarity of the transepithelial voltage in cortical collecting tubules from DOCA-treated animals. Thus adrenal mineralocorticoids may be necessary for maximal K secretion by the cortical collecting tubule, but they are not essential to maintain K secretion during "normal" K intake. In all groups K secretion is totally dependent on Na-K-ATPase. The lumen-positive transepithelial voltage from DOCA-treated animals after addition of ouabain suggests an additional effect of mineralocorticoid to stimulate secretion of cations (protons) or reabsorption of anions.
Na+-K+-ATPase inhibitors and renin release: relationship to calcium
Authors: Cruz-Soto M. , Benabe J. E. , Lopez-Novoa J. M. , Martinez-Maldonado M.
Published: December 2017

The inhibition of renin secretion and the vasoconstrictive action of cardiac glycosides may be attributed to increases in cytosolic calcium as a result of inhibition of Na+-K+-ATPase. These studies examined in the dog in vivo the role of calcium on the renal actions of ouabain as assessed from the modifying effects of calcium channel blockers. Since vanadate, another Na+-K+-ATPase, inhibitor, enhances in vitro the binding of ouabain to Na+-K+-ATPase, we examined the capacity of vanadate to modify the renal effects of ouabain in vivo. Infusion of ouabain (1 microgram X kg-1 X min-1) into the renal artery decreased RBF, GFR, and renin secretion, and produced diuresis and natriuresis. When ouabain was infused in dogs receiving the calcium channel blocker verapamil (100 microgram/min), it failed to suppress renin secretion or cause renal vasoconstriction. In addition, verapamil produced diuresis and natriuresis, which were greatly enhanced by ouabain (e.g., verapamil FENa 12.0 +/- 1.1----34.2 +/- 5.1%). The data strongly suggest that calcium entry into cells is a major mediator of the renin inhibitory effect and of the renal vasoconstriction induced by cardiac glycosides. The natriuresis observed during the calcium channel blocker infusion suggests that this drug may have a direct tubular effect on sodium reabsorption. Superimposition of vanadate (0.5 mumol/min) on ouabain infusion led to massive natriuresis (FENa, 5 +/- 1----35 +/- 4%), renal vasodilation (RBF 90 +/- 12----170 +/- 15 ml/min), and an increase in renin secretion (delta, 100%).(ABSTRACT TRUNCATED AT 250 WORDS)
Autoradiographic localization of benzodiazepine receptors in the rat kidney
Authors: Beaumont K. , Healy D. P. , Fanestil D. D.
Published: December 2017

The localization of benzodiazepine (BZD) receptors in the rat kidney was studied by autoradiography after in vitro labeling of kidney slices with flunitrazepam. The affinity, density, and rank order of displacement of [3H]-flunitrazepam by several BZDs (RO 5-4864 greater than diazepam greater than clonazepam) demonstrated that binding was to BZD receptors of the peripheral type. In autoradiograms obtained with tritium-sensitive film, a high density of silver grains was obtained in the outer medulla, with lower densities in the cortex. Binding was absent from the inner medulla (papilla). In higher resolution autoradiograms obtained with an emulsion-coated cover slip procedure, silver grains were seen to be concentrated over a tubular element in both outer medulla and cortex, identifiable by morphology and distribution as the thick ascending limb of the loop of Henle and the distal convoluted tubule. The identity of the labeled tubules was confirmed by immunofluorescent localization in adjacent slices of Tamm-Horsfall protein, a specific marker for these segments of tubules. Investigation of the effects of peripherally specific BZDs such as RO 5-4864 on distal tubule function is indicated.
Tissue-specific control of glandular kallikreins
Authors: van Leeuwen B. H. , Grinblat S. M. , Johnston C. I.
Published: December 2017

Glandular kallikreins are kinin-generating serine proteases found in the salivary glands, pancreas, reproductive organs, and kidney and in their secretions. They are physico-chemically, enzymatically, and immunologically identical but it is not known whether they perform similar functions at these separate anatomical sites. A specific radioimmunoassay was used to measure immunoreactive kallikrein in these tissues of the rat after various stimuli. Salt depletion significantly increased kallikrein in the kidney from 2.35 +/- 0.17 to 4.11 +/- 0.27 microgram/g tissue (P less than 0.01, 16 DF) and in the salivary glands from 16.8 +/- 2.1 to 24.2 +/- 0.9 mg/g tissue (P less than 0.01, 16 DF), but did not change pancreatic kallikrein. Deoxycorticosterone (2.4 mg s.c. over 8 days) led to a doubling in kidney kallikrein, from 2.35 +/- 0.17 to 5.27 +/- 0.56 microgram/g tissue (P less than 0.01, 18 DF), without changing salivary gland or pancreatic kallikrein, whereas testosterone (240 micrograms/day s.c. over 15 days) significantly increased salivary gland kallikrein from 26.6 +/- 2.1 to 42.2 +/- 1.8 mg/g tissue (P less than 0.01, 18 DF) with no increase in kidney or pancreatic kallikrein. Accordingly, the glandular kallikreins in these tissues vary independently, which suggests they are under different electrolyte and endocrine control and may perform different physiological functions at each anatomical site.
Sodium-dependent sulfate transport in renal outer cortical brush border membrane vesicles
Authors: Turner R. J.
Published: December 2017

The transport of sulfate into outer cortical brush border membrane vesicles (early proximal tubule) was studied. Sulfate uptake was markedly enhanced by sodium and slightly enhanced by lithium but showed no stimulation by other monovalent cations tested. Kinetic analysis of the sodium-dependent component of sulfate flux indicated a single transport system obeying Michaelis-Menten kinetics. Studies of the dependence of sulfate flux on sodium concentration indicated that more than one sodium ion was involved in the sulfate transport event. Although sulfate influx was found to be stimulated by negative intravesicular potentials, evidence is presented that sodium/sulfate cotransport is nevertheless an electroneutral event presumably involving 2 Na+ per SO2-4. Under zero trans sodium conditions sodium-dependent sulfate influx was stimulated by the presence of intravesicular unlabeled sulfate (trans stimulation); however, a similar stimulation of sulfate efflux by the presence of unlabeled extravesicular sulfate was not observed. These latter results are consistent with an ordered binding scheme for the transporter, with sulfate binding before sodium on the extravesicular (urine) surface and dissociating before sodium on the intravesicular (cytosolic) surface.
Evidence for electroneutral chloride transport in rabbit renal cortical brush border membrane vesicles
Authors: Shiuan D. , Weinstein S. W.
Published: December 2017

Controversial evidence exists as to whether electroneutral Cl-OH exchange occurs across the proximal tubular brush border membrane of the mammalian kidney. To help resolve this controversy, we carried out a series of experiments using rabbit renal cortical brush border membrane vesicles to determine the effect of changes in pH on 36Cl uptake across this membrane. Reducing pH equally inside and outside of the vesicle stimulated Cl-Cl exchange as well as chloride uptake. A proton gradient (out greater than in) stimulated and caused an overshoot in unidirectional Cl uptake. All three of these processes were inhibited by 4-acetoamido-4-isothiocyano-2,2-disulfonic stilbene. Valinomycin with K+ out-in added to shunt any proton diffusion potential, minimally inhibited pH gradient-dependent Cl uptake, and carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone (FCCP), added to increase the proton diffusion potential, minimally stimulated pH gradient-dependent Cl uptake. Sodium-glucose cotransport (an electrogenic system) was used to assess the efficacy of these ionophores. FCCP markedly enhanced and valinomycin markedly inhibited pH gradient stimulated sodium-glucose cotransport. Valinomycin added to vesicles with a 180/0 meq K+ out greater than in gradient stimulated less Cl uptake than a 6.0/7.5 pH out greater than in gradient. We conclude that these results provide strong evidence for the existence of an electroneutral Cl-OH exchanger or Cl-H symporter in this membrane.
Tubuloglomerular feedback-mediated decreases in glomerular pressure in Munich-Wistar rats
Authors: Bell P. D. , Reddington M. , Ploth D. , Navar L. G.
Published: December 2017

These experiments were performed to evaluate directly measured glomerular capillary pressure and single nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses in Munich-Wistar rats during increased distal flow rate achieved by infusing an isotonic electrolyte solution into unblocked late proximal tubules. Arterial pressure averaged 114 +/- 2 mmHg and proximal tubule pressure was 14 +/- 1 mmHg. In eight tubules, control SNGFR based on distal tubular fluid collections averaged 22 +/- 3 nl/min, decreased to 15 +/- 2.3 nl/min when 10-12 nl/min of perfusate was infused into the late proximal tubule, and further decreased to 9 +/- 1.7 nl/min at an infusion of 20-24 nl/min. In 22 tubules, control glomerular capillary pressure was 55 +/- 1.6 mmHg, decreased to 43 +/- 2.5 mmHg with addition of perfusate into a late proximal tubule at a rate of 24 nl/min, and returned to 53 +/- 3.1 mmHg when perfusion was stopped. In eight nephrons, glomerular capillary pressure was shown to be responsive to smaller increments in the late proximal infusion rate and was reduced by 4 +/- 0.5 and 7 +/- 1.1 mmHg at the intermediate rates of 10 and 15 nl/min, respectively. These results demonstrate that glomerular pressure decreases during increased distal delivery even when the tubule is not blocked. They are consistent with the hypothesis that increases in afferent arteriolar resistance are primarily responsible for feedback-mediated reductions in glomerular filtration rate.
Mutual dependence of sodium and chloride absorption by renal distal tubule
Authors: Velazquez H. , Good D. W. , Wright F. S.
Published: December 2017

Sodium transport and chloride transport by the renal distal tubule of rats were studied by in vivo continuous microperfusion to determine the effects of separately altering luminal sodium and chloride concentrations. Results showed that sodium absorption depends on luminal sodium concentration and chloride absorption depends on luminal chloride concentration; both relations are linear between approximately 10 and 100 mM and have slopes of approximately 2.5 pmol X min-1 X mM-1. Sodium absorption is also a saturable function of luminal chloride concentration, and chloride absorption is a saturable function of luminal sodium concentration; the half-maximal chloride and sodium concentrations are approximately 10 mM. Furosemide, 10(-4) M, when added to the fluid used to perfuse this segment inhibited sodium absorption and chloride absorption to a similar extent. Removal of chloride from luminal fluid (replaced with sulfate) and addition of furosemide to the perfusion fluid had little or no effect on the measured transepithelial voltage. The results are consistent with the presence of a mechanism in the luminal membrane of distal tubule cells that couples the absorptive transport of sodium and chloride.
Feedback pressure-flow responses in normal and angiotensin-prostaglandin-blocked rats
Authors: Persson A. E. , Gushwa L. C. , Blantz R. C.
Published: December 2017

We have examined the response of directly and indirectly (stop-flow) measured glomerular capillary hydrostatic pressure (PGC) and single nephron glomerular filtration rate (SNGFR) to increases in late proximal tubular flow rate in hydropenic rats and rats in which angiotensin II (ANG II) and prostaglandin generation was reduced by 3- to 5-day pretreatment with converting enzyme inhibitor (MK-421) and meclofenamate. In control rats, PGC (48 +/- 2 mmHg) decreased 9 +/- 1 mmHg when 25 nl/min was added to late proximal flow in unobstructed tubules, and PGC decreased 9 +/- 1 mmHg when late proximal perfusion rate was increased from 0 to 40 nl/min, incrementally, in wax-blocked tubules. The turning point or half-maximal response for PGC was at perfusion rates of 23 +/- 2 nl/min. Stop-flow estimated PGC (47 +/- 1 mmHg = control) responses were nearly identical. SNGFR decreased from 30 +/- 1 to 21 +/- 1 nl/min with increased perfusion in control rats. In ANG II-prostaglandin-blocked rats, PGC and stop-flow pressure responses were completely eliminated, yet SNGFR response persisted (36.2 to 28.0 nl/min) but to a somewhat lesser extent. Both direct and indirect PGC decrease with increases in late proximal flow rate in untreated rats. Studies in ANG II-prostaglandin-blocked rats suggest that tubuloglomerular feedback SNGFR responses can occur without changes in PGC, possibly via parallel changes in afferent and efferent arteriolar resistances.
Cell and luminal pH in the proximal tubule of Necturus kidney
Authors: Planelles G. , Kurkdjian A. , Anagnostopoulos T.
Published: December 2017

Double-barreled, selective microelectrodes filled with liquid ion exchanger were used to determine proximal tubule cell pH (pHcell), luminal pH (pHlum), and peritubular capillary blood pH (pHbl.pt) in Necturus kidney in vivo. The average pHbl.pt of 16 animals was 7.64 +/- 0.3; pHcell was 7.36 +/- 0.02 (n = 50), and pHlum was 7.50 +/- 0.05 (n = 16). Because of the variability in pHbl.pt from one animal to another, we studied the blood/cell/lumen pH differences. We sequentially measured with a single microelectrode pHcell and pHlum, and then pHbl.pt in an adjacent peritubular capillary. In 25 such paired determinations, the average pHbl.pt - pHcell difference was 0.28 +/- 0.03, cell acid, and the pHbl.pt - pHlum difference was 0.14 +/- 0.02, lumen acid. The pHcell in this series was significantly more acid than the pHlum (by 0.14 +/- 0.02), but in a few instances the pH gradient across the apical cell membrane was inversed. All measurements were performed in the initial portion of the proximal tubule. We conclude that 1) proximal cell pH is acid with regard to peritubular blood pH, 2) the proximal tubule of Necturus kidney is capable of establishing a small transepithelial pH difference (lumen acid), and 3) pHcell is generally more acid then pHlum.
Renal nerve activity in conscious rats during volume expansion and depletion
Authors: DiBona G. F. , Sawin L. L.
Published: December 2017

The role of renal nerve activity (RNA) in the renal response to isotonic saline volume expansion and furosemide-induced volume depletion was studied in conscious rats consuming a low (LNa), normal (NNa), or high (HNa) dietary sodium intake. In the control state, right atrial pressure (RAP) and UNa V were directly related and RNA was inversely related to dietary sodium intake, being 12.9 +/- 0.7, 10.9 +/- 1.1 and 8.7 +/- 0.6 units in LNa, NNa, and HNa rats, respectively. During volume expansion, RAP and UNa V increased and RNA decreased in all three dietary groups; however, the peak increase in UNa V was greater in the LNa (88 +/- 6 mueq/min) than NNa (34 +/- 9 mueq/min) or HNa (32 +/- 6 mueq/min) rats. The greater natriuresis in LNa was associated with a larger decrease in RNA in LNa (-6.1 +/- 0.5 units) than in NNa (-3.4 +/- 0.4 units). The greater contribution of inhibition of RNA to the increased natriuretic response to volume expansion in LNa compared with NNa rats was further examined in renal denervated animals. Bilateral renal denervation substantially reduced the natriuretic response to volume expansion in LNa rats (-70%) but had no significant effect in NNa rats (-15%). During volume depletion, RAP decreased, whereas UNa V and RNA increased in all three dietary groups. After the peak of the furosemide natriuresis, UNa V was lower in the LNa rats than in the NNa or HNa rats at any level of increased RNA, consistent with a role for the renal nerves in the normal renal adaptive response to sodium/volume depletion.(ABSTRACT TRUNCATED AT 250 WORDS)