bluuebunny/crossref_metadata_2025 huggingface dataset:
Parathyroid hormone and extrarenal acid buffering
Authors: Arruda J. A. , Alla V. , Rubinstein H. , Cruz-Soto M. , Sabatini S. , Batlle D. C. , Kurtzman N. A.
Published: December 2017

The role of parathyroid hormone (PTH) on the extrarenal buffering of an acid load was examined during HCl infusion (5 meq x kg-1 x h-1) to bilaterally nephrectomized rats. Thyroparathyroidectomized (TPTX) rats replaced with PTH had significantly higher blood pH and HCO3 values than TPTX rats not infused with PTH. Administration of EDTA, in a dose shown to release PTH, was associated with a significant increase in buffering capacity in intact but not in TPTX rats. Colchicine, given in a dose capable of stimulating PTH release, was also associated with enhanced buffering capacity in intact but not in TPTX rats. In TPTX rats infused with acetazolamide and PTH, the hormone failed to enhance extrarenal buffering of an acid load. Animals with chronic renal failure, induced by infarction of the kidney, also had an enhanced capacity to buffer an acid load. This enhanced buffering capacity in chronic renal failure was abolished by TPTX. Acute renal failure induced by bilateral ureteral ligation was also associated with increased buffering only in the presence of parathyroid glands. These data demonstrated that PTH, from either an exogenous or endogenous source, enhances extrarenal buffering capacity of an acid load. Chronic and acute renal failure are associated with increased buffering capacity, which is dependent on the presence of parathyroid glands. The data suggest that this effect is mediated through carbonic anhydrase.
Factors influencing chloride reabsorption in the collecting duct segment of the rat
Authors: Kirchner K. A. , Galla J. H. , Luke R. G.
Published: December 2017

To study factors influencing Cl reabsorption in the collecting duct segment of the rat, excretion of Cl and of 36Cl injected into late distal tubule segments of superficial nephrons were examined by microinjection and free-flow micropuncture techniques. Selective dietary Cl restriction for 7–10 days decreased urinary 36Cl recovery for microinjection [74 +/- 5% (SE)] compared with normal rats (90 +/- 3%, P < 0.01). Infusion of 0.15 M NaHCO3 (10% body wt) in the Cl-restricted rat led to marked increases in urinary flow rates and sodium excretion but did not increase 36Cl recovery. In these NaHCO3-infused rats, recovery of 36Cl was unaffected by increasing Cl concentration in the injectate from 40 to 140 peq/nl, but increased to levels not different from control (89 +/- 3%) when amphotericin B was included in the injectate. Equivalent infusion of 0.15 M NaCl in the Cl-restricted rats also increased 36Cl recovery to control levels (89 +/- 3%). This response was not altered by administration of DOCA. Absolute chloride delivery to late distal tubule sites was not different in NaCl- and NaHCO3-expanded groups, and (TF/UF)Cl was less in the NaHCO3 group (0.27 +/- 0.03 vs. 0.37 +/- 0.02, P < 0.05); therefore, the chemical gradient for Cl did not favor Cl efflux. There was a significant correlation between urinary recovery of 36Cl and urinary Cl excretion in the NaCl- and NaHCO3–expanded animals. It is suggested that Cl restriction alters, by an as yet unknown mechanism that is independent of changes in Na balance, the intrinsic Cl-absorbing capacity of the collecting duct.
Induction of amiloride-sensitive sodium transport in the rat colon by mineralocorticoids
Authors: Will Peter C. , Lebowitz Jonathan L. , Hopfer Ulrich
Published: December 2017

Page F261: Peter C. Will, Jonathan L. Lebowitz, and Ulrich Hopfer. “Induction of amiloride-sensitive sodium transport in the rat colon by mineralocorticoids.” Page F267: the second equation in the appendix should read

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Chloride transport inhibition by piretanide and MK-196 in bullfrog corneal epithelium
Authors: Candia O. A. , Schoen H. F. , Low L. , Podos S. M.
Published: December 2017

Two new diuretic agents, piretanide and MK-196, inhibited short-circuit current (SCC) across the isolated frog corneal epithelium. The effect is explained as an inhibition of active Cl transport. A definite decrease in SCC and an increase in electrical resistance was observed with both diuretics in concentrations as low as 10(-6) M. Piretanide, at 10(-4) M, reduced the SCC by 90%, reduced th unidirectional forward Cl flux from 0.60 to 0.28 mueq x h-1 x cm-2, and increased the resistance by 60%. There was no effect on the Cl backflux. At 10(-4) M, MK-196 reduced the SCC by 83% and increased the resistance by 72%, from 1.68 to 2.91 k omega x cm2. Replacement of Cl by SO4 in the bathing solutions resulted in a larger increase in resistance, from 1.68 to 3.80 k omega x cm2. The diuretics had no effect on active Na transport across the corneal epithelium. After the permeability of the apical side was increased by amphotericin B, the drugs could not inhibit the Cl-originated SCC. These results suggest that piretanide and MK-196 selectively inhibit active Cl transport in the cornea by blocking Cl permeability of the apical side of the epithelial cells.
Renal function during reflexly activated catecholamine flow through an adrenorenal rete
Authors: Katholi R. E. , Bishop S. P. , Oparil S. , James T. N.
Published: December 2017

Reflex vasoconstriction that occurs in the kidney of the dog can be the result of either of two mechanisms. The first is by activation of the renal sympathetic nerves and the second by reflex activation of catecholamine flow through an adrenorenal rete. Both reflex mechanisms can be activated by transient hypotension caused by experimentally induced atrial fibrillation in the sodium-replete pentobarbital-anesthetized dog. This study was undertaken to measure and compare the magnitude of changes in renal function that occur when these reflex mechanisms are activated and to evaluate the possible role of intrarenal angiotensin II in these two reflex effects. Reflex activation of catecholamine flow through an adrenorenal rete in intact or denervated kidneys produced a 26 +/- 3% decrease in renal plasma flow, a 23 +/- 4% decrease in glomerular filtration rate, a 58 +/- 7% decrease in urinary sodium excretion, and a 4 +/- 1% increase in filtration fraction, but no change in the fractional distribution of intrarenal blood flow. Changes of a similar direction and magnitude were seen in the same animals during reflex activation of the renal sympathetic nerves in the kidneys with intact or ligated adrenorenal rete. The same studies were performed after the intrarenal action of angiotensin II was blocked with [Sar1,Ala8]angiotensin II and similar responses were seen. Both of these reflexes appear to be important mechanisms by which the kidney can maintain vascular volume, and neither depends on intrarenal angiotensin II activity.
Direct renal tubular effects of choline on electrolyte excretion in the chicken
Authors: Besseghir K. , Rennick B.
Published: December 2017

Direct local effects of choline on electrolyte effects did not reappear. Acetylcholine was more potent than choline in producing the electrolyte effects. These results suggest that choline-induced changes in renal electrolyte excretion are mediated by a muscarinic receptor completely separate from the choline transport system. These effects imply that choline is not an "inert" cation.
Acid excretion by bicarbonate-free perfused rat kidney
Authors: Garvey M. H. , Maude D. L.
Published: December 2017

We measured titratable acid (TA) and NH4 excretion by isolated rat kidneys perfused either with conventional bicarbonate-containing solutions or with solutions in which bicarbonate was replaced by propionate. Rates of TA excretion by bicarbonate-perfused kidneys were similar to in vivo values, 0.27 +/- 0.04 mueq.ml GF-1 (0.21 mueq.min-1.g-1), and increased significantly under bicarbonate-free conditions to 0.70 +/- 0.12 mueq.ml GF-1 (0.42 mueq.min-1.g-1). At the same time the perfusate/urine pH difference (delta pH) increased significantly, from 0.63 +/- 0.06 to 0.92 +/- 0.06. Carbonic anhydrase inhibition by 5 X 10(-4) M acetazolamide alkalinized the urine of bicarbonate-perfused kidneys, while in the bicarbonate-free preparation the urine remained acid (delta pH = 0.27 +/- 0.04) and titratable acid continued to be excreted, though at a reduced rate, 0.19 +/- 0.04 mueq.ml GF-1. Under these same bicarbonate-free carbonic anhydrase-inhibited conditions, lowering the perfusate pH from 7.4 to 7.1 increased delta pH to 0.36 +/- 0.02 and caused total acid excretion (TA + NH4) to rise from 0.29 +/- 0.04 to 0.45 +/- 0.06 mueq.ml GF-1, and increasing the perfusate [HPO4] from 2.4 to 9.6 mM increased TA to 0.80 +/- 0.09 mueq.ml GF-1.
Dual effect of carbonic anhydrase inhibitors on H+ transport by the turtle bladder
Authors: Norby L. H. , Bethencourt D. , Schwartz J. H.
Published: December 2017

Previous studies in isolated turtle bladder have demonstrated that high concentrations of carbonic anhydrase (CA) inhibitors limit H+ transport (JH) by reducing the catalyzed rate of CO2 hydroxylation and also by inhibiting some other step in the acidification process. One possibility is that these inhibitors alter the energy substrate requirement for JH. Recent work has demonstrated that JH may be dependent in part on glucose oxidation via the pentose shunt (PS). The present study was undertaken to determine whether CA inhibitors exert a direct effect on PS metabolism by turtle bladder. Acetazolamide and benzolamide at concentrations of 5 X 10(-4) M significantly reduced the rate of 14CO2 evolution from [1–14C]- but not [6–14C]glucose after JH was abolished by an adverse electrochemical gradient for JH+. These changes are consistent with a reduction in PS metabolism. These same sulfonamides also reduced glucose-6-phosphate dehydrogenase (G-6-PD) activity in mucosal cell homogenates. Acetazolamide decreased the Vmax of G-6-PD but not the Km and, therefore, appears to be a noncompetitive inhibitor of G-6-PD with an estimated Ki of 10(-4) M. The t-butyl analogue of acetazolamide, CL 13850, which is without CA inhibitory activity, had no measurable effect on G-6-PD activity. Accordingly, it is suggested the sulfonamide CA inhibitors may reduce JH by two modes of action, inhibition of CA and inhibition of G-6-PD.
Meclofenamate and urine concentration with and without exposure of the renal papilla
Authors: Roman R. J. , Lechene C.
Published: December 2017

The recent finding that inhibitors of prostaglandin synthesis prevent the fall in urine concentration produced by papillary exposure challenges the hypothesis that contact between the pelvic urine and papilla is essential to the renal concentrating process. The present study examines the change in urine osmolality produced by exposure of the renal papilla in rats given meclofenamate. In control animals urine osmolality(Uosmol) decreased 57% after 2 h of exposure of the renal papilla. In rats given meclofenamate 4 mg/kg urine osmolality increased 16%, urine flow decreased 30%, and glomerular filtration rate was unchanged in the nonexposed kidney. Meclofenamate, however, did not alter the decrease in Uosmol seen in the kidney with the exposed papilla. Meclofenamate 10 mg/kg was also ineffective in preventing the fall in urine osmolality produced by papillary exposure, although this higher dose decreased glomerular filtration rate and arterial blood pressure. These results are consistent with the finding that pelvic urine urea is important to the urinary concentrating process and with the hypothesis that urine osmolality falls after papillary exposure because contact between pelvic urine and papilla is interrupted.
Distal tubular sodium reabsorption in the developing rat kidney
Authors: Aperia A. , Elinder G.
Published: December 2017

The immature kidney has a blunted natriuretic response to saline loading. to localize the high fractional Na reabsorption in the developing nephron, we determined Na delivery to the early distal tubule (EDT) and the fraction of filtered Na remaining in the tubular fluid [(TF/P)Na/In] in the EDT and late distal tubule (LDT) in 24- and 40-day-old hydropenic (HP) and volume-expanded (VE) rats. During HP the (TF/P)Na/In ratio in EDT was significantly higher in the younger rats (12.6 +/- 2.0%) than in the older rats (4.2 +/- 0.6%), but because of a lower SNGFR in the younger rats th Na delivery to EDT was the same in both age groups. The (TF/P)Na/In ratio in LDT was not different in 24- and 40-day-old HP rats (1.1 +/- 0.4 and 1.7 +/- 0.3%, respectively). During VE th (TF/P)Na/In ratio in LDT was significantly lower in 24- (3.0 +/- 0.7%) than in 40-day-old rats (8.3 +/- 1.1%). The (TF/P)Na/In ratio in LDT correlated well with the urinary fractional Na excretion. It is concluded that the Na reabsorption capacity of the developing nephron is more efficient in the distal tubule than in the more proximal tubular segments.
Adrenergically induced renin release in conscious indomethacin-treated dogs and rats
Authors: Seymour A. A. , Davis J. O. , Echtenkamp S. F. , Dietz J. R. , Freeman R. H.
Published: December 2017

To investigate the role of endogenous prostaglandins in renin release stimulated via adrenergic pathways, isoproterenol, norepinephrine (NE) and NE in the presence of phentolamine (PTA) were infused into conscious sodium-replete rats and dogs. Isoproterenol (1 microgram.kg-1.min-1) infusion into intact rats increased plasma renin activity (PRA) eightfold. AFter pretreatment with the prostaglandin (PG) cyclooxygenase inhibitor indomethacin (5 mg/kg), isoproterenol increased PRA 16-fold. In dogs, isoproterenol (0.4 microgram.kg-1.min-1) increased PRA six-fold before indomethacin and 11-fold during PG inhibition. Infusion of NE into both rats (250 ng.kg-1.min-1) and dogs (1 microgram.kg-1.min-1) failed to increase PRA before indomethacin, but during inhibition of PG synthesis NE increased PRA in both species. During partial alpha-adrenergic blockade with PTA in dogs, PTA alone increased PRA by 38% and NE given during PTA infusion increased PRA further both before indomethacin by twofold and during PG inhibition by fivefold. In rats given NE during PTA infusion, PRA increased only after indomethacin injection. Additionally, in dogs the renin responses to these adrenergic agents were even greater after indomethacin administration than before the drug. These results in both conscious rats and dogs give no indication that renal prostaglandins mediate the renin response to adrenergic stimulation.
Effect of vanadate on renal tubular function in rats
Authors: Westenfelder C. , Hamburger R. K. , Garcia M. E.
Published: December 2017

Orthovanadate (VO4) has been shown to cause a marked natriuresis in rats. This has been ascribed to its inhibitory action on renal Na-K-ATPase activity. Because virtually all nephron segments possess Na-K-ATPase activity the administration of VO4 should alter renal tubular transport along the entire nephron. To examine this possibility, adult rats were anesthetized and infused with VO4 (10 mumol.kg body wt-1.h-1 i.v.). This dose had no effect on glomerular filtration rate, effective renal plasma flow, and blood pressure, whereas urine flow and sodium and water excretion rose markedly. Potassium excretion remained unaltered. VO4 depressed only maximal bicarbonate and glucose reabsorption without causing a glucose or bicarbonate "leak" at normal levels of blood glucose or bicarbonate. In acutely thyroparathyroidectomized rats VO4 produced a striking phosphaturia, not accompanied by an increase in nephrogenous cAMP excretion. Both free water clearance in Brattleboro rats and free water reabsorption in normal rats was significantly depressed by VO4. These data demonstrate that VO4 depresses tubular reabsorption in proximal and distal nephron segments. We conclude that VO4 exerts its effect on tubular function by inhibition of Na-K-ATPase activity.
Na intake, renal renin, and the severity of myohemoglobinuric renal failure in rats
Authors: Bidani A. K. , Churchill P. C.
Published: December 2017

We have examined the role of dietary Na and renal cortical renin concentration (RCRC) on the severity of glycerol-induced acute renal failure (ARF) in the rat. Na loading (1% NaCl to drink) and Na deprivation (Na-free diet) of 5-6 wk duration decreased and increased RCRC, respectively, with respect to control. As assessed by blood urea nitrogen measured 48 h after glycerol injection, the severity of ARF was inversely related to RCRC. However, this was not a causal relationship. Either 6- or 48-h access to 1% NaCl did not lower RCRC of previously Na-deprived rats, but did decrease the severity of ARF. Conversely, 6- or 48-h access to tap water did not increase RCRC of previously Na-loaded rats, but did increase severity of ARF. A significant inverse correlation was found between severity of ARF and Na excretion prior to glycerol injection, a finding consistent with the hypothesis that solute diuresis has a protective effect.
Cimetidine secretion by rabbit renal tubules in vitro
Authors: McKinney T. D. , Myers P. , Speeg K. V.
Published: December 2017

Cimetidine, a drug in widespread use in the treatment of peptic ulcer disease, is eliminated primarily via urinary excretion. We examined cimetidine transport by rabbit proximal straight tubules perfused in vitro. [3H]Cimetidine in the bath was actively secreted into the tubule lumen. There was a curvilinear relationship between the rate of cimetidine secretion and the concentration of bath cimetidine. Cimetidine secretion was inhibited by hypothermia and ouabain. Quinine, tolazoline, probenecid, phloridzin, creatinine, p-aminohippurate, and cimetidine sulfoxide inhibited cimetidine secretion in a dose-related manner. At low cimetidine concentrations lumen-to-bath transport rates were only 11-18% of bath-to-lumen secretory rates. High performance liquid chromatographic analysis of collected tubular fluid showed a predominance of cimetidine and a small amount of cimetidine sulfoxide in ratios similar to those of the bath. These studies show that cimetidine is actively secreted into the lumen of rabbit proximal straight tubules in vitro. Secretion probably occurs via the organic base and to a lesser extent the acid transport systems.
Renal transport of NAP-taurine
Authors: Stokols M. F. , Koschier F. J. , Goldinger J. M. , Hong S. K.
Published: December 2017

The renal transport of N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate (NAP-taurine), a potential photoaffinity label, was studied using the rabbit renal cortical slice and the isolated perfused rat kidney. NAP-taurine inhibited the slice accumulation of PAH in a dose-dependent manner (ID50 = 2.5 X 10(-5) M). It accumulated to a steady-state slice-to-medium concentration ratio of 14. However, NAP-taurine was not toxic to the tissue, as it did not influence the accumulation of the organic cation tetraethylammonium. NAP-taurine transport was saturable and its accumulation was inhibited by the metabolic inhibitors PAH, probenecid, 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), ouabain, and the absence of sodium. Kinetic studies showed that the Km for NAP-taurine is 3.5 X 10(-5) M, and also that PAH competitively inhibits NAP-taurine influx with a Ki of 1.2 X 10(-3) M. Experiments with the rat isolated perfused kidney gave the NAP-taurine-to-inulin clearance ratio of approximately 5, indicating net tubular secretion. DIDS significantly reduced this clearance ratio to 0.8. The results suggest NAP-taurine is handled by the kidney in a manner analogous to PAH and may thus be useful as a photoaffinity label for the renal organic anion transport system.
Functional characteristics of the renal interstitium
Authors: Wolgast M. , Larson M. , Nygren K.
Published: December 2017

The renal interstitial space analyzed as "inulin space" comprises about 13% in the rat. The Starling forces of this compartment are governed by the balance between tubular and capillary fluid transport and also by the leakage of plasma proteins from the blood side. Protein transport will occur in a large-pore system in the peritubular capillary membrane. During control antidiuresis, the interstitial hydrostatic pressure is 2-4 mmHg. The colloid osmotic pressure shows a larger variability but is generally about 5 mmHg. During conditions of depressed capillary reabsorption but unchanged tubular reabsorption, as in saline expansion, the interstitial hydrostatic pressure rises 3-4 times, whereas the colloid osmotic pressure will show a steep fall resulting from the increased fluid entry and unchanged protein transport. The interstitial volume increases only slightly, since it is compressed by the expanding tubules. The influence of interstitial physical forces on tubular transport remains unclear, mainly due to the inaccessibility of the lateral interspaces to direct measurement of relevant parameters.
Epithelial organization and hormone sensitivity of toad urinary bladder cells in culture
Authors: Johnson J. P. , Steele R. E. , Perkins F. M. , Wade J. B. , Preston A. S. , Green S. W. , Handler J. S.
Published: December 2017

Two continuous cell lines (TB-M and TB-6c) derived from epithelial cells of the toad urinary bladder form epithelia in culture that manifest hormone-sensitive transepithelial transport. Development of transepithelial electrical resistance (R) and transport rate (ISC) are dependent on time and density of cells seeded, but steady-state ISC and R are characteristic for each cell line and independent of seeding density. Some responses of intact toad bladder are preserved in culture, whereas others are altered or absent. Neither cell line responds to vasopressin. Analogues of cAMP increase sodium transport and urea permeability in both cell lines but do not affect water permeability. The intramembrane particle aggregates associated with the vasopressin- and cAMP-induced increase in water permeability of the intact bladder could not be detected in the cell lines. Aldosterone increases sodium transport in both cell lines, and the time course and concentration dependence of the response to aldosterone are similar to those of the intact bladder. The relative effect of a series of steroids on ISC reveals corticosterone to be a more potent mineralocorticoid in cultured cells than in the intact bladder.
Dissociation of saline-induced natriuresis from urea washout in the rat
Authors: Gennari F. J. , Johns C. , Caflisch C. R. , Cortell S.
Published: December 2017

Medullary urea washout has been postulated to play a major role in the natriuretic response to volume expansion (VE). To examine this hypothesis, renal tissue solute composition was measured in a natriuretic and nonnatriuretic model of VE. Renal tissue composition was analyzed during hydropenia, acute VE, acute VE with renal artery pressure reduced to 70 mmHg at the onset of saline loading (immediate clamping), and acute VE with renal artery pressure reduced to 70 mmHg after 45 min of saline loading (delayed clamping). Immediate clamping, a nonnatriuretic model of VE, prevented VE-induced urea washout and the increase in sodium and water content in the cortex and outer medulla. Delayed clamping, a natriuretic model of VE, produced a pattern of tissue composition very similar to immediate clamping. Tissue urea content was not significantly different in the two protocols and only minor differences in sodium and water content were noted. Thus, under these experimental conditions, VE-induced natriuresis can be dissociated from medullary urea washout, and other mechanisms must be invoked to explain the increased sodium excretion.
Altered prostaglandin synthesis by glomeruli from rats with unilateral ureteral ligation
Authors: Folkert V. W. , Schlondorff D.
Published: December 2017

There is evidence that prostaglandins modulate renal hemodynamics in unilateral ureteral obstruction. We examined prostaglandin synthesis by glomeruli from rats with 24- and 72-h unilateral ureteral ligation. During prelabeling of the lipid pools with [14C]arachidonate glomeruli from the ligated kidney incorporated less 14C label than those from contralateral or normal control kidneys. However, the incorporation of [14C]arachidonate into phospholipids of glomeruli was proportionately higher in the ligated kidney. Incubation of the prelabeled glomeruli with either angiotensin II or bradykinin significantly increased release of labeled prostaglandins and turnover of [14C]arachidonate on the ligated side. Radioimmunoassay determinations showed that after 24-h ligation, glomeruli from both sides produced comparable amounts of PGF2 alpha, 6-keto-PGF1 alpha, TXB2, and PGE2. After 72 h, glomeruli from the ligated kidney produced more PGF2 alpha, 6-keto-PGF1 alpha, and TXB2 than the contralateral glomeruli. In contrast, PGE2 synthesis was higher in contralateral glomeruli. Neither angiotensin II nor bradykinin had a measurable effect on radioimmunoassayable prostaglandins. We conclude that unilateral ureteral ligation is associated with specific alterations of glomerular prostaglandin synthesis and phospholipid metabolism that are intrinsic to the glomerulus.
Renal and systemic acid-base effects of chronic hypoparathyroidism in dogs
Authors: Hulter H. N. , Toto R. D. , Bonner E. L. , Ilnicki L. P. , Sebastian A.
Published: December 2017

MEtabolic alkalosis has been reported in patients with chronic hypoparathyroidism under conditions of uncontrolled diet and medication intake. Hypoparathyroidism has also been reported to result in increased renal bicarbonate reabsorptive capacity in acutely bicarbonate-loaded dogs. However, the acid-base effects of experimentally induced chronic hypoparathyroidism have not been investigated in any species. Accordingly, we investigated the chronic effects of hypoparathyroidism by thyroparathyroidectomy (TPTX) plus thyroxine replacement on renal regulation of plasma acid-base composition under metabolic balance conditions of normal dietary acid load (group I) and alkali load (group II, 9.0 meq/kg HCO3(-) daily) in dogs ingesting a normal Cl-, high Ca2+ diet throughout study. For groups I and II pre-TPTX: [HCO3(-)]p, 19.7 +/- 1.0, 20.1 +/- 0.9 meq/liter. Plasma acid-base composition (days 5-10) was unchanged by TPTX: delta [HCO3(-)]p, -0.7 +/- 0.4, 0.0 +/- 0.2 meq/liter; delta [H+]p, 0 +/- 1, -1 +/- 0 neq/liter, NS from control. A reduction in plasma total calcium concentration ([CaT]p) occurred and persisted (group I: [CaT]p, -1.6 +/- 0.2 mg/100 ml, P less than 0.01, day 1 and -1.2 +/- 0.9, days 5-10; group II: -1.4 +/- 0.3 mg/100 ml, P less than 0.01, day 1 and -2.3 +/- 0.4, days 5-10). No significant change in net acid or Cl- excretion occurred following TPTX. Thus, chronic hypoparathyroidism characterized by a chronic reduction in [CaT]p does not result in significant alterations in renal regulation of plasma acid-base composition in the dog.
Functional and morphologic patterns of renal maturation in the developing guinea pig
Authors: Merlet-Benichou C. , Pegorier M. , Muffat-Joly M. , Augeron C.
Published: December 2017

Clearance experiments were carried out in fetal, young, and adult pigs undergoing salt loading. Kidney sections were histologically examined and the proximal tubular length, glomerular volume, and number of glomeruli were estimated. Between days 48 and 55 of gestation, the significant increase in glomerular filtration rate was proportionately higher than the concentration increase in water, total solutes, and sodium reabsorption. During this period, neither the proximal tubular length nor the glomerular volume of the juxtamedullary nephrons changed significantly. The main morphologic change took place in the superficial cortex, where new glomeruli attached to very short tubules differentiated. From day 55 to birth, the increase in water, total solutes, and sodium filtered loads was proportionately smaller than the concomitant increase in tubular reabsorption. During this phase, the major morphologic change was the significant lengthening of the proximal tubules of the juxtamedullary and superficial nephrons. These findings suggest that for water, sodium, and total solutes the maturation of superficial nephrons is accompanied by a phase of functional glomerular preponderance. Despite the differentiation of the superficial nephrons, renal handling of normally filtered glucose did not change significantly. Functional glomerulotubular coupling for water, sodium, and total solutes took place soon after birth.
Multiple sites for interaction of prostaglandin and vasopressin in toad urinary bladder
Authors: Schlondorff D. , Carvounis C. P. , Jacoby M. , Satriano J. A. , Levine S. D.
Published: December 2017

The interaction of vasopressin with prostaglandins were examined in the toad bladder by determining water flows, cAMP levels, and cAMP-dependent protein kinase activity. Both water flow and activation of cAMP-kinase in response to vasopressin were enhanced after prostaglandin inhibition, consistent with inhibition of vasopressin-induced cAMP generation by endogenous prostaglandins. On the other hand exogeneous PGE stimulated cAMP generation. PGE1 (10(-7) M) alone did not increase water flow but activated kinase more than vasopressin only. Addition of PGE1 (10(-7) M) and vasopressin inhibited water flow as compared with vasopressin along but increased the kinase ratio above that with vasopressin only. PGE2 (10(-5) M) increased the cAMP content and kinase ratio even more than vasopressin but again resulted in no water flow. Addition of vasopressin and PGE2 (10(-5) M) increased water flow but did not alter cAMP content or the kinase ratio compared with PGE2 alone. Similar results were obtained with PGE1. Accordingly, prostaglandin dissociates cAMP levels and kinase ratio from the hydroosmotic response, suggesting that PGE2 inhibits steps distal to cAMP. Consistent with this, in bladders pretreated with naproxen or meclofenamate, PGE2 (10(-8) to 10(-6) M) inhibited the response to submaximal doses of cAMP (5 mM) or 8-bromo-cAMP (0.03 mM). Furthermore, pretreatment with naproxen significantly enhanced the response to cAMP (5 mM). These studies provide evidence for vasopressin-PGE interaction at the site of cAMP generation and also at a step(s) unrelated to cAMP generation.
Organic solutes in fluid absorption by renal proximal convolutes tubules
Authors: Burg M. , Patlak C. , Green N. , Villey D.
Published: December 2017

Page 627: M. Burg, C. Patlak, N. Green, and D. Villey. “Organic solutes in fluid absorption by renal proximal convolutes tubules.” Page 628: the equation in the right column should read

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Studies of the urinary acidification defect induced by lithium
Authors: Bank N. , Lief P. D. , Aynedjian H. S. , Mutz B. F.
Published: December 2017

Experiments were carried out in rats and isolated turtle bladders to study the defect in H+ transport induced by LiCl. After 3-4 days of intraperitoneal LiCl, rats developed urinary findings of "distal" renal tubular acidosis. Proximal tubular fluid pH measured in situ by glass microelectrodes was higher in lithium-treated rats than in acidotic controls. Proximal fluid total CO2 [tCO2] was also higher, and the fraction of tCO2 leaving the proximal tubule was 14 vs. 7% (P less than 0.001). Impaired acidification was also apparent beyond distal convoluted tubules, as judged by normal distal tCO2 reabsorption but increased HCO3(-) in the urine. During NaHCO3 loading, the proximal defect was ameliorated but not the distal. Turtle bladder studies showed that mucosal lithium inhibits H+ secretion secondary to reducing transepithelial electrical potential, presumably by hyperpolarization of the luminal membrane. A similar mechanism may be responsible for lithium's effect on the distal nephron. Inhibition of proximal tubular HCO3(-) reabsorption is probably not attributable to electrical potential changes but might be due to interference of luminal membrane Na+ entry by Li+ and reduced (Na+ + Li+)-H+ exchange.
Effect of ventilatory rate on renal venous PGE2 and PGF2 alpha efflux in anesthetized dogs
Authors: Lonigro A. J. , Brash D. W. , Stephenson A. H. , Heitmann L. J. , Sprague R. S.
Published: December 2017

In anesthetized laparotomized male mongrel dogs with ventilatory rate set at 10 breath.min-1, tidal volume was adjusted so that control arterial pH and PCO2 were within the normal range for unanesthetized dogs. Control renal venous PGE2 and PGF2 alpha concentrations were comparable to those of unanesthetized dogs, namely, 57 +/- 10 and 114 +/- 18 pg.ml-1, respectively. In contrast, control arterial plasma renin activity (PRA), 6.6 +/- 1.2 ng.ml-1.h-1, was considerably greater than in unanesthetized dogs. Stepwise increases in ventilatory rate increased renal venous PGE2 and PGF2 alpha to 109 +/- 18 and 205 +/- 41 pg.ml-1, respectively. Hyperventilation reduced PCO2 and increased pH and PRA but had no effect on renal blood flow, arterial blood pressure, or arterial PGE2 and PGF2 alpha concentrations. When the ventilatory rate was returned to control levels, pH, PCO2, PRA, and renal venous PGE2 and PGF2 alpha concentrations returned to control. Ventilatory rate or some consequence of altering ventilatory rate is, therefore, a determinant of renal venous efflux of PGE2 and PGF2 alpha. Moreover, it may be a more important determinant of "resting" concentrations of prostaglandins in renal venous blood than anesthesia, laparotomy, or PRA.
Distribution of two model amino acids from cerebrospinal fluid to brain and blood
Authors: Fenstermacher J. D. , Davson H.
Published: December 2017

Ventriculocisternal perfusions of anesthetized rabbits were performed for 1-3 h with solutions containing radioactively labeled alpha-aminoisobutyric acid (AIB), cycloleucine (CYCL), and sucrose. Serial brain samples were taken at the conclusion of the perfusion period and assayed for radioactivity. Tissue concentration profiles were constructed from these data; tissue distribution spaces and diffusion coefficients (Dt) plus brain capillary transfer constants were estimated from the profiles. The Dt of sucrose was somewhat larger at 1 h than at 2 and 3 h. Tissue distribution spaces of 300-400% were found with AIB after 3 h. Inclusion of 5 mM AIB in the perfusate produced markedly lower tracer AIB spaces. The tissue distribution spaces of CYCL ranged from 100 to 400% and depended on the concentration of CYCL in the perfusate. A brain-to-blood transfer half time of 7.5 min was measured for CYCL. These findings demonstrate that sizable cellular uptake of CYCL and AIB occurs, that these processes are concentration dependent, and that the rates of influx and efflux across brain capillaries are similar.
Hemodynamic and renal functional changes after acute unilateral nephrectomy in the dog: role of carotid sinus baroreceptors
Authors: Ayus J. C. , Humphreys M. H.
Published: December 2017

We examined the role of the carotid sinus baroreceptors in the hemodynamic and renal functional changes initiated by acute unilateral nephrectomy (AUN). In 15 anesthetized dogs, AUN caused increases in sodium (UNaV) and potassium excretion (UKV) without significant changes in GFR, renal blood flow, or mean arterial pressure. Cardiac output (CO) was measured in five of these animals and decreased from 2.5 +/- 0.2 to 1.9 +/- 0.3 liter/min as total peripheral resistance (TPR) increased. In 11 dogs with bilateral acute surgical carotid sinus denervation, AUN failed to cause any change in renal hemodynamics, UNaV, or UKV that could be distinguished from sham-operated time controls. CO was measured in seven of these dogs and also did not change. AUN caused an immediate, transient elevation in blood pressure that returned to control levels 15 min after nephrectomy. When bilateral carotid occlusion (BCO) was carried out prior to AUN in animals with intact carotid sinus baroreceptors, AUN again caused an immediate increase in blood pressure but no changes in CO or electrolyte excretion. In separate studies, AUN increased UNaV and UKV significantly; when BCO was then carried out after AUN, cation excretion remained elevated. In seven dogs undergoing continuous perfusion of the carotid circulation bilaterally at constant pressure, AUN again failed to increase cation excretion despite a 30 mmHg rise in arterial blood pressure. These studies demonstrate that AUN fails to initiate hemodynamic or compensatory renal functional changes in dogs with bilateral carotid sinus denervation or in animals in which intact baroreceptors are shielded from the systemic circulation by BCO or perfusion at constant pressure, indicating the importance of these baroreceptors in the early changes after AUN.
Transport of potassium in the rabbit pars recta
Authors: Work J. , Troutman S. L. , Schafer J. A.
Published: December 2017

Unidirectional fluxes of 42K+ and 86Rb+ were measured in isolated perfused segments of proximal straight tubules and no differences were found between the two isotopes for the same flux determination. In the three segments examined (the early and late superficial proximal straight tubule and the juxtamedullary proximal straight tubule) there was apparent net active K+ secretion as demonstrated by differences in the unidirectional fluxes of 2.6, 3.2, and 4.8 pmol.min-1.mm-1, respectively. However, in contrast to the expectations for active K+ secretion, the bath-to-lumen fluxes were unaffected by 0.1 mM ouabain added to the bathing solution, and in the early superficial and juxtamedullary segments these fluxes were directly proportional to the K+ concentration of the bathing solution over a range of concentrations. Apparent K+ permeability coefficients were calculated from lumen-to-bath fluxes to be 0.14 +/- 0.02, 0.10 +/- 0.02, and 0.52 +/- 0.07 micrometers.s-1 in the early and late superficial and juxtamedullary segments, respectively. Based on these data and on a mathematical analysis, we have concluded that active K+ secretion of the magnitude measured would have little importance in determining the K+ load delivered to the descending limb of the loop of Henle. However, the higher passive permeability of the juxtamedullary segment would allow significant net K+ secretion if the outer medullary interstitium had even a moderately elevated K+ concentration.
Mechanism of distal tubular chloride transport in Amphiuma kidney
Authors: Oberleithner H. , Guggino W. , Giebisch G.
Published: December 2017

To characterize the mechanism of chloride transport across individual cell membranes, experiments were carried out on early distal tubules in the doubly perfused Amphiuma kidney and net chloride flux, transepithelial and transmembrane cell potentials, and intracellular chloride activity measured. Net chloride flux was evaluated by a modified stationary microperfusion technique, and intracellular and intraluminal chloride activities by means of double-barreled liquid ion exchange microelectrodes. Control conditions were characterized by significant net volume and chloride reabsorption, a transepithelial potential difference of +9.0 +/- 0.5 mV (lumen positive), and cell chloride activities above electrochemical equilibrium across both luminal and peritubular cell membranes. Following luminal application of furosemide (5 X 10(-5) M) or perfusion with either a sodium- or chloride-free solution, net flux of chloride fell dramatically, the transepithelial potential difference was abolished, and cell chloride activity dropped sharply to approach electrochemical equilibrium. The decrease in transepithelial potential difference was fully accounted for by hyperpolarization of the basolateral cell membrane potential. These results are consistent with a furosemide-sensitive, electrically neutral sodium chloride cotransport mechanism across the luminal cell membrane.
Direct evaluation of the permeability of the rat proximal convoluted tubule to CO2
Authors: Lucci M. S. , Pucacco L. R. , Carter N. W. , DuBose T. D.
Published: December 2017

Conflicting data exist regarding the ability of the rat proximal convoluted tubule to maintain a transepithelial gradient for CO2 and the effects of carbonic anhydrase on CO2 permeability. The present in vivo microperfusion experiments were designed to assess the ability of the rat proximal tubule to sustain a CO2 gradient between tubule lumen and peritubular blood. Tubules were perfused at rates ranging from 10 to 100 nl/min with isotonic sodium chloride containing no CO2. Peritubular capillary and intraluminal PCO2 was measured during microperfusion with PCO2 microelectrodes to allow determination of the transepithelial CO2 gradient. The mean PCO2 measured in peritubular capillaries of control rats was 60.6 +/- 1.9 mmHg. Since the perfusion solution initially contained no CO2, a gradient of 60 mmHg was imposed across the tubule epithelium. Intraluminal PCO2 rapidly approached that of the surrounding capillaries. At a tubule perfusion rate of 20 nl/min, the gradient between lumen and blood decreased to 0.9 mmHg, a value not significantly greater than zero. The calculated CO2 permeability coefficient (KCO2) was 3.69 X 10(-5) cm2/s. Addition of either 10(-4) M acetazolamide or benzolamide did not prolong the rapid dissipation of the imposed CO2 gradient. The KCO2 during carbonic anhydrase inhibition was not significantly different from control values. It is concluded that the rat proximal tubule does not present a physiologically significant diffusion barrier to CO2 either in the presence or absence of carbonic anhydrase activity. The previously demonstrated acid disequilibrium pH in the proximal tubule during inhibition of carbonic anhydrase represents an intraluminal accumulation of carbonic acid rather than of carbon dioxide gas.
Role of renal alpha-adrenoceptors mediating renin secretion
Authors: Osborn J. L. , DiBona G. F. , Thames M. D.
Published: December 2017

The increase in renin secretion resulting from low-frequency renal nerve stimulation (0.5 Hz) occurs in the absence of changes in urinary sodium excretion or renal blood flow and is apparently derived from a direct effect of renal sympathetic nerves on juxtaglomerular granular cells. We sought to determine the role of renal alpha-adrenoceptors in this neurally evoked renin secretion. The neurally evoked renin secretion was unaffected by renal alpha-adrenoceptor blockade with phentolamine or prazosin; however, two dose levels of phenoxybenzamine equally inhibited the renin secretion. The renal vasoconstrictor response to graded renal nerve stimulation was similarly diminished by phentolamine, prazosin, and the higher phenoxybenzamine dose, whereas the lower phenoxybenzamine dose was significantly less effective. Renal alpha-adrenoceptor stimulation with methoxamine infusion at doses that were just subthreshold for altering renal blood flow and urinary sodium excretion or at doses that just reduced urinary sodium excretion also did not change renin secretion. Higher doses of methoxamine that decreased both renal blood flow and sodium excretion increased renin secretion. Based on the inability of phentolamine and prazosin to prevent neurally mediated renin secretion and on the dose-response relationship between methoxamine and changes in renin secretion, renal blood flow, and urinary sodium excretion, we conclude that renal alpha-adrenoceptors do not mediate renin secretion elicited by direct neural activation of the juxtaglomerular granular cells. The data suggest that phenoxybenzamine inhibits neurally mediated renin secretion by a mechanism other than renal alpha-adrenoceptor blockade.
Renal responses to prolonged central volume expansion in conscious primates
Authors: Kass D. A. , Moore-Ede M. C.
Published: December 2017

Urinary and hormonal responses to prolonged central vascular volume expansion induced by 4 days of continuous lower body positive air pressure (LBPP) were examined in conscious, chair-acclimatized squirrel monkeys. The initial 12 h of exposure to LBPP (20 mmHg) induced a marked natriuresis, diuresis, kaliuresis, and decrease in urine osmolality. During the subsequent 4 days of LBPP stimulation, the acute natriuresis gradually declined by 75%, whereas potassium excretion completely returned to control rates after 24 h. In contrast, the diuresis and decrease in osmolality persisted, although there were significant circadian variations in urine flow (as well as sodium and potassium excretion) produced by a marked nocturnal suppression of renal responses to LBPP. Plasma aldosterone and potassium concentration both decreased acutely following LBPP initiation; however, aldosterone levels subsequently returned to normal range during continued LBPP exposure, whereas plasma potassium remained low until the pressure stimulus was terminated. These results indicated that prolonged central volume expansion induced both a sustained natriuresis and diuresis; however, chronic adaptation limited net fluid and electrolyte losses through the first 24 h of LBPP exposure. The loss of potassium appeared to be a consequence of the initial diuresis and natriuresis induced by LBPP, rather than being directly mediated by aldosterone.
Impaired energy metabolism in rat myocardium during phosphate depletion
Authors: Brautbar N. , Baczynski R. , Carpenter C. , Moser S. , Geiger P. , Finander P. , Massry S. G.
Published: December 2017

The effects of phosphate depletion (PD) of 4, 8, and 12 wk duration on myocardial energy metabolism were studied in rats fed a phosphate-deficient diet and compared with rats pair-fed a normal phosphate diet. Myocardial biopsies were examined for high-energy phosphate bonds. The results show that PD causes a significant reduction in myocardial concentration of inorganic phosphorus at 4 wk of PD and creatine phosphate at 8 wk of PD, while adenine nucleotides were significantly reduced only after 12 wk of PD. The changes in cellular inorganic phosphorus and creatine phosphate displayed a significant correlation with serum phosphorus levels. Mitochondrial respiration was impaired early in PD. Total cellular, mitochondrial, and myofibrillar creatine kinase activities were significantly reduced at 4 wk of PD and fell further at 8 and 12 wk. These data show that chronic PD is associated with reduced mitochondrial capacity to produce ATP, impaired transport via the creatine phosphate shuttle, and reduced myofibrillar ability to utilize ATP. These abnormalities indicate that all steps of myocardial energetics are impaired in PD and provide the molecular basis for the altered myocardial function seen in PD.
Selective inhibition by epinephrine of parathyroid hormone-stimulated adenylate cyclase in rat renal cortex
Authors: Woodcock E. A. , Johnston C. I.
Published: December 2017

Parathyroid hormone- (PTH) stimulated adenylate cyclase activity in homogenates of rat renal cortex was inhibited by l-epinephrine. The specificity of the inhibition indicated that it was mediated by alpha 2-receptors. The inhibition of PTH-stimulated activity was greater than the inhibition of basal activity. The absolute decrease in adenylate cyclase activity produced by 10-4 M l-epinephrine was from 16.3 +/-0.6 (SE) to 11.2 +/- 0.6 pmol.min-1.mg-1 for activity stimulated by 10 microgram/ml PTH. Basal activity was decreased from 2.3 +/- 0.07 to 1.7 +/- 0.04. A similar inhibition of PTH-stimulated adenylate cyclase by l-epinephrine was demonstrated in preparations of renal cortical tubules. In contrast, the quantitative decrease in vasopressin-or calcitonin-stimulated activity by 10-4 M l-epinephrine was the same as the decrease in basal activity. These results demonstrate that PTH receptors that stimulated adenylate cyclase and alpha 2-adrenergic receptors that inhibit adenylate cyclase are present on the same cells in the renal tubules. Thus, a mechanism exists whereby alpha-adrenergic agonists can oppose the tubular actions of PTH via a direct inhibition of adenylate cyclase activity.