bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of vasopressin in hypertension: studies using the Brattleboro rat
Authors: Woods R. L. , Johnston C. I.
Published: December 2017

Plasma arginine vasopressin (AVP) levels were elevated in both one-kidney, one-clip [1K-1C) and two-kidney, one-clip (2K-1C) hypertensive Long-Evans rats. Homozygous Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI), which are completely devoid of vasopressin, were made hypertensive using the 1K-1C Goldblatt models for renal hypertension. The 2K-1C DI rats developed hypertension at the same rate and to the same degree as normal 2K-1C hypertensive Long-Evans rats. The development of hypertension in 1K-1C DI rats was similar to the normal 1K-1C hypertensive Long-Evans rats. However, the absolute levels of systolic blood pressure reached were significantly less in the vasopressin-deficient rats. Treatment with 1-desamino-8-D-arginine vasopressin (DDAVP), the synthetic analogue of arginine vasopressin that has high antidiuretic but low pressor potencies, was associated with restoration of water balance in the volume-depleted DI rats and also restored blood pressure to hypertensive levels equivalent to the 1K-1C Long-Evans rats. These studies suggest that vasopressin is not essential for the development of experimental renal hypertension in rats but may contribute to the absolute levels of systolic blood pressure reached through its properties as an antidiuretic hormone.
Bicarbonate reabsorption in the papillary collecting duct: effect of acetazolamide
Authors: Richardson R. M. , Kunau R. T.
Published: December 2017

The present study was designed to characterize bicarbonate (total CO2) reabsorption in the papillary collecting duct of the kidney of the Munich-Wistar rat when total CO2 delivery to this segment was increased by the systemic infusion of a bicarbonate-rich solution. Additional studies examined the effect of the systemic administration of acetazolamide, a carbonic anhydrase inhibitor, on total CO2 reabsorption. Employing free-flow micropuncture techniques, tubular fluid samples were obtained from the base and tip of the exposed papilla and subsequently analyzed for total CO2 and inulin. Total CO2 reabsorption increased in a linear fashion, approximating 34% of that delivered to the base, as total CO2 delivery increased from 3 to 20% of the filtered load. When examined at comparable absolute rates of total CO2 delivery (mumol/min) to the papillary collecting duct, acetazolamide administration resulted in marked inhibition of total CO2 reabsorption. The results of these studies suggest that the papillary collecting duct of the rat kidney possesses a significant capacity for reabsorption of total CO2 and that this reabsorption is diminished by the administration of acetazolamide.
Independence of the acute acid-buffering response from endogenous parathyroid hormone
Authors: Madias N. E. , Johns C. A. , Homer S. M.
Published: December 2017

Two recent reports have made the provocative suggestion that parathyroid hormone (PTH) and, by implication, bone play a critical role in the early phase of acid buffering. The purpose of the present study was to investigate the effect of PTH on the acute buffering process by examining the influence of thyroparathyroidectomy (TPTX) on acid-base parameters in nephrectomized rats following infusion of hydrochloric acid at two differing doses. To ensure hemodynamic and physiologic stability of the animals, the required surgical procedures were staged over several days. Additionally, the experimental protocol was carried out in awake and unrestrained animals. Non-TPTX (sham) animals underwent a sham operation to equalize the surgical stresses between the two groups. The decrements in plasma [HCO-3] observed following infusion of 3.5 mmol/kg HCl over 1 h did not differ between TPTX vs. sham animals at 1 h (-9.4 vs. -9.9 meq/liter), 3 h (-8.6 vs. 8.6 meq/liter), or 6 h (-8.6 vs. -8.5 meq/liter) from the start of the infusion. Similarly, virtually identical falls in plasma [HCO-3] were observed between TPTX vs. sham rats after infusion of 5 mmol/kg HCl over 30 min at 30 min (-13.6 vs. -14.2 meq/liter) and 3 h (-10.9 vs. -11.4 meq/liter) after the start of the infusion. At both doses, the resultant changes in plasma [H+] and PaCO2 were not different in the two groups. The observed mortality was comparable in both TPTX and sham groups. The data demonstrate that endogenous PTH is not necessary in the early phase of buffering of a mineral acid load.
Analysis of adrenergic effects of the anesthetics Inactin and alpha-chloralose
Authors: Tucker B. J. , Peterson O. W. , Ziegler M. G. , Blantz R. C.
Published: December 2017

Renal and systemic adrenergic system responses were examined and compared under conditions of Inactin, a barbiturate, and alpha-chloralose anesthesia in hydropenic Munich-Wistar rats. Base-line plasma norepinephrine and other catecholamine levels were higher in Inactin-anesthetized rats. Norepinephrine was infused to raise blood pressure 15-20 mmHg above base line and plasma norepinephrine was again significantly higher with Inactin. In another group, angiotensin II was infused into the cerebral lateral ventricle in both Inactin- and alpha-chloralose-anesthetized rats, a method of stimulating centrally activated adrenergic output. After central stimulation, mean arterial pressure increased only in alpha-chloralose-anesthetized rats. Micropuncture studies examining systemic and glomerular hemodynamics were performed in alpha-chloralose- and Inactin-anesthetized rats before and after the infusion of phentolamine, an alpha-adrenergic antagonist. Infusion of phentolamine decreased mean arterial pressure to a significantly greater extent in the Inactin-anesthetized rats, suggesting a greater base-line systemic alpha-adrenergic activity with Inactin anesthesia. However, renal afferent and efferent arteriolar resistances were not significantly different after phentolamine, and any trend for resistances to decrease could be explained by autoregulation. Inactin increases systemic adrenergic activity, but renal vascular resistances are not significantly affected by this increased activity.
Renin release selectively stimulated by prostaglandin I2 in isolated rat glomeruli
Authors: Beierwaltes W. H. , Schryver S. , Sanders E. , Strand J. , Romero J. C.
Published: December 2017

Renal glomeruli were isolated from rat kidneys using a passive mechanical sieving technique. Glomerular microsomal fraction, glomerular homogenate, or intact glomeruli were incubated with [1-14C]arachidonic acid, and the profile of prostaglandin (PG) synthesis was determined by thin-layer chromatography. The three incubation systems produced 15.3, 20.8, and 40.4% 6-keto-PGF1 alpha; 19.1, 23.5, and 15.3 PGF2 alpha; 5.7, 9.1, and 3.9% thromboxane (TX) B2; 36.0, 35.1, and 37.0% PGE2; and 23.9, 11.3, and 3.4% PGD2, respectively. Glomeruli were placed in suspension within glass chambers and superfused with Krebs solution. Superfusion with 1.6 x 10(-4) M arachidonic acid stimulated a significant release of renin from glomeruli, whereas 2.7 x 10(-6) M PGE1, PGE2, PGF2 alpha, TXB2, PGD2, or a stable analog of PGH2 had no effect on renin. When the rapid breakdown of PGI2 was counteracted by either increasing the concentration to 1.7 x 10(-4) M or stabilizing in Krebs at pH 9.4, it stimulated a significant increase in renin release. Reducing the arachidonic acid concentration to 1.6 x 10(-5) M eliminated both renin release and PGI2 synthesis, while increased PGE2 synthesis persisted. Finally, using an inhibitor of PGI2 synthesis, azo analog 1 (2.8 x 10(-6) M), 6-keto-PGF1 alpha produced in response to arachidonic acid was eliminated, as was the concurrent release of renin, but PGE2 synthesis was not affected. These results suggest that the mechanism of direct interaction between renal PG and renin in isolated glomeruli is selectively due to the action of PGI2.
Stimulation of renin secretion by vasoactive intestinal peptide
Authors: Porter J. P. , Reid I. A. , Said S. I. , Ganong W. F.
Published: December 2017

Vasoactive intestinal peptide (VIP) increased plasma renin activity (PRA) in pentobarbital-anesthetized dogs. A 15-min infusion of VIP directly into the renal artery at a dose of 33 ng . kg-1 min-1 increased renin secretion rate from 1,461 +/- 393 to 5,769 +/- 1,794 ng ANG I . ml-1 . 3 h-1 . min-1, and increased PRA from 19.2 +/- 2.3 to 29.2 +/- 4.7 ng ANG I . ml-1 . 3 h-1. Renal blood flow and creatinine clearance were also increased, whereas plasma potassium concentration and diastolic blood pressure decreased. There was no change in sodium or potassium excretion. When administered intravenously, 33 and 13 ng . kg-1 . min-1 VIP increased PRA. A dose of 3.3 ng . kg-1 . min-1 failed to increased PRA when given intravenously but produced a significant increase in PRA from 22.8 +/- 8.1 to 40.5 +/- 19.4 ng ANG I . ml-1 . 3 h-1 when infused into the renal artery. This increase occurred without any change in plasma potassium concentration or blood pressure. Renin secretion was increased by a two- to threefold increase in plasma VIP; comparable increases in plasma VIP have been reported to be produced by various experimental procedures. The data indicate that VIP increases renin secretion. The peptide appears to act directly on the kidney and may act directly on the juxtaglomerular cells.
Lack of solvent drag of NaCl and NaHCO3 in rabbit proximal tubules
Authors: Jacobson H. R. , Kokko J. P. , Seldin D. W. , Holmberg C.
Published: December 2017

Using in vitro microperfusion of rabbit nephron segments we measured the effects of osmotically induced water flow on net transport of HCO3 and Cl. Measurements were made in superficial and juxtamedullary proximal convolutions and in superficial pars recta. In addition, measurements were taken in the presence and absence (hypothermia) of active transport. Using osmotic gradients of 25 mM raffinose in superficial and 50 mM in juxtamedullary segments, we observed increases in water flow equal to or greater than the normal rates of volume reabsorption observed in these tubule segments. However, there were no significant changes in HCO3 and Cl flux. This lack of significant solvent drag was seen both when osmotic water flow was in the lumen-to-bath direction and when osmotic flow was in the bath-to-lumen direction. The results of these studies suggest that solvent drag does not contribute significantly to NaCl and NaHCO3 reabsorption in proximal tubules. The lack of significant solvent drag of these salts can be interpreted as indicating either that osmotically induced transepithelial water flow in proximal tubules almost exclusively traverses transcellular pathways or that proximal tubule tight junction reflection coefficients for these salts are close to unity.
Mechanism of hypoalbuminemia in the 7/8-nephrectomized rat with chronic renal failure
Authors: Kaysen G. A. , Watson J. B.
Published: December 2017

Hypoalbuminemia has been observed consistently in patients and experimental animals with chronic renal failure (CRF). A defect in albumin synthesis, catabolism, or distribution has been invoked as the cause, but there is no agreement as to which, if any, of these disorders results from the uremic state. We studied albumin homeostasis in 7/8-nephrectomized rats with CRF. Serum albumin concentration was lower in CRF (29.6 +/- 4.59 mg/ml) than in sham-operated control rats (36.3 +/- 4.3 mg/ml). Albumin synthesis, determined directly by measuring incorporation of 14CO2 into arginine in albumin, was increased in CRF rats as was total albumin clearance, measured using 125I-albumin disappearance. Rats with CRF were albuminuric. Albumin synthesis was increased by the amount necessary to replace urinary losses, but net albumin catabolism was the same as in control animals. Albuminuria was prevented by addition of excess tryptophan to the diet. Total albumin clearance and albumin synthesis were the same in these tryptophan-fed CRF animals as in CRF sham-operated animals, but these CRF rats were still hypoalbuminemic (33.6 +/- 5.27 vs. 36.3 +/- 4.3 mg/ml). Rats with CRF were plasma volume expanded. Institution of a low-sodium diet at the time of partial nephrectomy prevented plasma volume expansion and albuminuria as well. Serum albumin concentration, albumin distribution, pool sizes, and total albumin clearance remained the same as in CRF sham-operated animals. Hypoalbuminemia in CRF rats is due to two factors. Plasma volume expansion with pool dilution contributes 40% of the decrease and external albumin losses resulting from albuminuria contribute the other 60%. Albumin synthesis, catabolism, and distribution are intact.
Glaphenine-induced acute renal failure in the rat: a new experimental model
Authors: Ganeval D. , Grunfeld J. P. , Eloy L. , Lacour B. , Russo-Marie F. , Noel L. H. , Anagnostopoulos T.
Published: December 2017

Glaphenine, a nonsteroid analgesic compound, administered by gastric gavage in rats (800 mg/kg), induced nonoliguric reversible acute renal failure (ARF). Intratubular deposits were found in medullary collecting ducts. Intratubular hydrostatic pressure (Pt) increased from 11.7 +/- 0.7 to 30.0 +/- 0.9 mmHg. Renal failure was almost completely prevented by concomitant high water and solute diuresis, achieved by furosemide infusion in Wistar rats and by high salt intake in Brattleboro rats with diabetes insipidus. In the latter protected animals, Pt was only slightly elevated (17.0 +/- 0.5 mmHg). Urinary excretion of prostaglandin E2 (PGE2) dropped dramatically after glaphenine administration in Wistar rats; the fall was slight in Brattleboro rats in which PGE2 excretion was normally low. We conclude that tubular obstruction plays a prominent role in glaphenine-induced ARF in the rat. High water and solute diuresis prevented tubular obstruction. Reduced renal PGE2 synthesis is probably not involved in the pathophysiology of this ARF model, inasmuch as Brattleboro rats on a high salt intake were protected despite low basal urinary excretion of PGE2.
Direct analysis of the effector mechanism of the tubuloglomerular feedback system
Authors: Ichikawa I.
Published: December 2017

The determinants of single nephron glomerular filtration rate (SNGFR) were examined in Munich-Wistar rats by direct glomerular micropuncture during orthograde perfusion of the same nephron's loop of Henle with isotonic Ringer solution at O and 40 nl/min. At the higher loop flow rate, SNGFR decreased significantly by approximately 35% relative to the nonperfused condition. Whereas indirect stop-flow estimates of mean glomerular capillary hydraulic pressure (PGC) also decreased significantly by approximately 8 mmHg, directly measured PGC values were found to be unaffected by the change in loop flow rate. Instead, both glomerular plasma flow rate (QA) and the ultrafiltration coefficient were found to decrease significantly at the higher loop flow rate, thereby accounting for the measured reduction in SNGFR. Given the observed near constancy of directly measured PGC and significant reduction in QA, both afferent and effect arteriolar resistances were calculated to increase in response to the higher loop perfusion rate. In a separate set of experiments, it was demonstrated that cessation of glomerular filtration increased directly measured PGC in the condition of zero loop perfusion but not when the loop was perfused at a high flow rate. These results indicate 1) that tubuloglomerular feedback-induced changes in SNGFR are not accompanied by changes in PGC; and 2) that tubuloglomerular feedback regulation of GFR is mediated by alterations in vasomotor tone of preglomerular, glomerular, and postglomerular microvessels. 3) Based on the close anatomical contact between mesangial cells and these vessels, a single effector mechanism channeled through mesangial contractility is suggested.
Effect of imidazole on the recovery from bilateral ureteral obstruction in dogs
Authors: Cadnapaphornchai P. , Bondar N. P. , McDonald F. D.
Published: December 2017

The effects of indomethacin (INDO) and imidazole (IMID) on postobstructed kidney functions were evaluated in dogs after 24 h of bilateral ureteral obstruction (BUO). In vehicle-treated dogs 1 h after release of BUO, clearances of inulin and PAH (Cin and Cpah) were 37 and 26%, respectively, of the preobstruction values. Fractional sodium excretion (FEna) increased from 0.5 +/- 0.1 to 2.9 +/- 0.6. Urine osmolality (Uosmol) increased by 55 +/- 9 mosmol/kg H2O in response to 50 mU of aqueous vasopressin. In INDO-treated dogs, Cin and Cpah were 39 and 21%, respectively, of the preobstruction values. FEna increased from 0.7 +/- 0.2 to 4.0 +/- 0.9. Uosmol increased by 91 +/- 19 mosmol/kg H2O in response to vasopressin. This lack of beneficial effects of INDO may reflect its cancelling effect on prostaglandins' and thromboxanes' (TX) effects on the renal hemodynamics of the postobstructed kidney. To further assess the roles of TX in the postobstructed kidney, IMID, and inhibitor of TX synthesis, was given before the release of obstruction. In this group of dogs, the Cin of the postobstructed kidney did not differ from the preobstruction value. CC pah was 45% of the preobstruction value, a level significantly higher than in either vehicle- or INDO-treated dogs. FEna wa 1.5 +/- 0.2 before and 3.5 +/- 2.3 after obstruction. Uosmol increased by 187 +/- 51 mosmol/kg H2O after vasopressin, a level significantly higher than in vehicle-treated dogs. The present study suggests that IMID improves Cin, Cpah, FEna, and concentrating ability of the postobstructed kidney. TX may be responsible for the persistent reductions of Cin and Cpah in the postobstructed kidney.
Renal Na+-K+-ATPase in renin release
Authors: Cruz-Soto M. A. , Benabe J. E. , Lopez-Novoa J. M. , Martinez-Maldonado M.
Published: December 2017

The effects of ouabain and furosemide on renin secretion, renal function, and renal Na+-K+-ATPase were investigated in anesthetized dogs. Furosemide (2 mg/kg) induced significant diuresis, natriuresis, an increase in renal blood flow (RBF), and a fivefold increase in renin secretory rate (RSR), but no changes in glomerular filtration rate (GFR). Infusion of ouabain (1 microgram . kg-1 . min-1) into one renal artery during furosemide diuresis increased fractional sodium excretion from 22 +/- 2 to 30 +/- 3% from the ipsilateral kidney but did not change urine flow, RBF, or GFR, whereas RSR fell to control values (698 +/- 203 to 137 +/- 43). When ouabain preceded furosemide, the rise in RBF and RSR induced by furosemide was abolished but sodium excretion increased. Ouabain infused in vivo inhibited Na+-K+-ATPase in microsomal fractions from cortex (34%) and medulla (27%) as compared with control. Neither saline nor furosemide exerted any effect on Na+-K+-ATPase. Moreover, the effect of ouabain alone on Na+-K+-ATPase was not different from that of ouabain plus furosemide. No changes in Mg2+-ATPase were detected in any of the experiments. These results indicate that inhibition of renal Na+-K+-ATPase abolishes furosemide-induced renin secretion despite potentiation of the natriuretic effect of the diuretic. It is apparent that the level of activity of Na+-K+-ATPase is of prime importance for renin secretion. In addition, ouabain may act directly on the juxtaglomerular cells to inhibit renin secretion.
Effect of adrenal enucleation on inner medullary collecting duct function in the rat
Authors: Bengele H. H. , Alexander E. A.
Published: December 2017

Page F453: H. H. Bengele and E. A. Alexander. “Effect of adrenal enucleation on inner medullary collecting duct function in the rat.” Page F456: The following acknowledgment should be added: The accomplishment of this work was helped by the National Biotechnology Resource in Electron Probe Microanalysis, Claude Lechene Director, Harvard Medical School. This work was supported by Grant 5-P41-RR00679 from the National Institutes of Health.
Organic anion infusions exacerbate experimental acute renal failure
Authors: Zager R. A. , Johannes G. A. , Sharma H. M.
Published: December 2017

This investigation proposed to determine whether high organic anion (OA) loads per nephron increase renal susceptibility to acute ischemic and nephrotoxic injury. Anesthetized Sprague-Dawley rats were infused with a control infusate, Na2SO4, or an OA (hippurate, p-aminohippurate, cephalothin; 0.125-1.0 mg/min). After a 40-min control period, acute renal injury was induced by either bilateral renal pedicle cross-clamping (X25 min) or by HgCl2 administration (12 mg/kg i.v.). Glomerular filtration rate (clearance of [125I]iothalamate) was determined every 20 min before and after renal injury. Non-OA-infused rats lost 51 +/- 4% (ischemia) and 40 +/- 4% (HgCl2) of control GFR. OA infusion exacerbated this loss of renal function (ischemia, 89 +/- 2%; HgCl2, 84 +/- 4%). Renal histology demonstrated that OA-treated acute renal failure (ARF) rats had more vacuolar degeneration of proximal tubular cells (HgCl2, ischemia) and greater tubular dilatation (ischemia) than did non-OA-treated ARF rats. These functional and histologic responses to OA infusion were not OA dose dependent. Discontinuation of OA infusion did not cause a subsequent rise in GFR. Na2SO4 infusion had no detrimental effects on ischemic ARF. Control rats subjected to prolonged OA infusion (1 mg/min X 5 h) maintained stable GFR and had normal renal histology. ARF rats infused with low-dose cephalothin had terminal serum cephalothin concentrations within a range commonly seen in humans. Conclusion: organic anion infusions can exacerbate early functional and histologic parameters of experimental ARF.
Factors causing natriuresis after hypothalamic injection of a cholinergic drug in rats
Authors: Silva-Netto C. R. , Jackson R. H. , Colindres R. E.
Published: December 2017

We investigated possible mechanisms for the natriuresis seen after injection of the cholinergic drug carbamylcholine chloride (carbachol) into the lateral hypothalamus of conscious rats. In unrestrained rats injection of 1 microgram of carbachol in 1 microliter of 0.15 M NaCl solution through a permanently implanted cannula produced a significant natriuresis and kaliuresis. Injection of vehicle produced no changes. The same animals were then subjected to bilateral renal denervation (n = 13) or sham denervation (n = 13) and injected with the same solutions 1 wk later. Carbachol injection produced a natriuresis (P less than 0.0001) and a kaliuresis (P less than 0.01) in all animals studied. Both responses were of a magnitude similar to the responses seen before denervation. We studied other rats while awake but restrained, which permitted the performance of clearance studies and blood pressure measurements. Injection of carbachol produced diuresis, natriuresis, and kaliuresis in all rats, with no change in p-aminohippurate clearance and only transient change in inulin clearance. An increase in blood pressure occurred in some but not all rats. The response in rats with bilaterally denervated kidneys (n = 7) was similar to that of rats with innervated kidneys (n = 5). The natriuresis seen after cholinergic stimulation of the hypothalamus in conscious rats is not primarily mediated by inhibition of renal nerve activity and can be dissociated from changes in blood pressure, glomerular filtration rate, and renal plasma flow.
Renal denervation in the rat: analysis of glomerular and proximal tubular function
Authors: Pelayo J. C. , Ziegler M. G. , Jose P. A. , Blantz R. C.
Published: December 2017

We examined 1) the potential modifications in both single nephron filtration rate (SNGFR) and the determinants of glomerular ultrafiltration, and 2) the alterations in peritubular capillary (PTC) "physical factors" that may contribute to changes in proximal tubular reabsorption (APR) after acute renal denervation (DNx). Micropuncture measurements were obtained in euvolemic Munich-Wistar rats with DNx or sham operation (sham). The content of norepinephrine in renal tissue homogenates was markedly reduced in DNx kidneys compared with sham kidneys (P less than 0.001). Mean arterial blood pressure, hematocrit, whole kidney GFR, and urinary flow rate were not different between the sham and DNx groups. Absolute urinary sodium excretion was 3 times greater in the DNx than in the sham group (P less than 0.01). SNGFR and its determinants were not statistically different in the two experimental conditions. APR was significantly reduced by approximately 25% in DNx (P less than 0.02). This reduction in APR was not accompanied by significant directional changes in peritubular capillary and renal interstitial pressures and the passive driving forces acting across the PTC-proximal tubular epithelium. These data demonstrate that elimination of renal innervation does not alter SNGFR or its determinants and suggest that the effect of denervation on APR is a primary epithelial event that occurs independent of changes in renal interstitial pressure and peritubular oncotic and hydrostatic pressures.
Effect of potassium concentration on bicarbonate reabsorption in the rabbit proximal convoluted tubule
Authors: Sasaki S. , Berry C. A. , Rector F. C.
Published: December 2017

The direct effects of acute changes in K+ concentration on HCO-3 (JnettCO2) and volume reabsorption (Jv) were examined in isolated perfused rabbit proximal convoluted tubules (PCT). Increasing ambient K+ concentration from 5 to 8 mM did not change JnettCO2 (94.5 +/- 16.1 vs. 98.8 +/- 17.7 pmol X mm-1 X min-1) or Jv (1.27 +/- 0.15 vs. 1.24 +/- 0.16 nl X mm-1 X min-1). In contrast, reducing ambient K+ concentration from 5 to 2 mM inhibited JnettCO2 by 22% and Jv by 29%. Reducing luminal K+ concentration from 5 to 0 mM with constant bath K+ concentration at 5 mM did not affect JnettCO2 or Jv. Further reductions in bath K+ concentration to 0.5 and 0 mM showed a similar dependence of both fluxes on K+ concentration. Half-maximum inhibition of JnettCO2 was obtained at 1.1 mM ambient K+ concentration and of Jv at 0.85 mM. At zero bath K+ concentration JnettCO2 was 6.6 +/- 2.5 pmol X mm-1 X min-1 and Jv was 0.03 +/- 0.04 nl X mm-1 X min-1. To determine whether this rate of acidification was significantly different from zero, we examined the ability of the PCT to generate tCO2 concentration gradients with zero bath K+ concentration at slow perfusion rates. The tCO2 concentration gradient generated (0.94 mM) was not different from that found when the perfusate was inserted directly into the collection pipette in the absence of a tubule (0.71 mM). These data are consistent with the view that HCO-3 reabsorption is totally dependent on the Na+-K+-ATPase pump system.
Stimulation by antidiuretic hormone of electrolyte tubular reabsorption in rat kidney
Authors: de Rouffignac C. , Corman B. , Roinel N.
Published: December 2017

The effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on renal excretion and tubular transport of water and electrolytes were investigated in homozygous DI Brattleboro rats. To ascertain these effects on the loop of Henle, circulating glucagon, parathyroid hormone, and thyrocalcitonin were reduced before the experiments, as these hormones are believed to stimulate the same cells of the thick ascending limb as ADH. dDAVP did not alter either glomerular or proximal tubular functions. In the loop, it consistently raised reabsorption of Mg, Ca, K, and, to a lesser extent, Na and Cl, but phosphate transport was not affected. dDAVP lowered the urinary excretion rates for Mg, Ca, K, Cl, and total solutes. For Mg, this reduction was independent of the drop in the urinary flow rate following dDAVP administration but was significantly correlated to this drop in the case of Ca, K, Cl, and total solutes. Na and P excretions were not altered by dDAVP. It is concluded that, in vivo, administration of ADH 1) stimulates reabsorption of Na, Cl, Mg, Ca, and K by the thick ascending limb, 2) consistently enhances Mg reabsorption by the whole kidney by enhancing reabsorption in the loop of Henle, and 3) at maximal antidiuresis, raises Ca, K, Cl, and total solute reabsorption, probably because of the drop in tubular flow rates in the distal parts of the nephron consequent to the hormone administration.
Bicarbonate transport in cortical and outer medullary collecting tubules
Authors: Lombard W. E. , Kokko J. P. , Jacobson H. R.
Published: December 2017

The collecting ducts are thought to represent a low-capacity high-gradient acidification system. However, the inaccessibility of the various regions of the collecting duct system has prevented direct segmental analysis of its contribution to distal acidification. The present in vitro microperfusion studies compare bicarbonate transport (in pmol . mm-1 . min-1) in rabbit cortical (CCT) and outer medullary collecting tubules (MCT) perfused and bathed with symmetrical Ringer bicarbonate solution at pH 7.4. Cortical segments from normal animals exhibited no net bicarbonate transport (-2.15 +/- 1.93) whereas MCT from normal animals reabsorbed bicarbonate at a rate of 11.3 +/- 1.4. Both bicarbonate reabsorption and the lumen-positive voltage (+9.4 +/- 1.1 mV) in MCT were totally inhibited by 10(-4) M acetazolamide. CCT from NH4Cl-treated rabbits demonstrated significant bicarbonate reabsorption (1.8 +/- 0.7) when perfused at slow rates. CCT harvested from animals given a NaHCO3 load for 48 h prior to death secreted bicarbonate (-6.2 +/- 2.5). These studies confirm earlier observations of the ability of the CCT to reabsorb or secrete bicarbonate. In addition, they demonstrate significant axial heterogeneity in acidification in the collecting duct system and identify the outer medullary collecting tubule from inner stripe of outer medulla as a segment of major capacity.
Endogenous opioids and electrolyte excretion after contralateral renal exclusion
Authors: Ribstein J. , Humphreys M. H.
Published: December 2017

Acute reductions in functioning renal mass result in increases in both sodium (U Na V) and potassium (U K V) excretion by the contralateral kidney (CK). We studied the role of endogenous opioids in this response. In control experiments acute unilateral nephrectomy (AUN) increased U Na V from 1,788 +/- 1,125 (SD) to 3,939 +/- 1,819 and U K V from 1,385 +/- 561 to 2,254 +/- 832 neq/min by the CK (P less than 0.005 for both); similar results occurred in rats undergoing acute unilateral ureteral occlusion (UUO). These increases occurred without overall change in GFR or mean arterial pressure. In rats receiving a continuous infusion of the opiate-receptor antagonist naloxone (0.3 mg . kg-1 . h-1) neither AUN nor UUO produced significant alterations in U Na V or U K V by the CK; naloxone infusion by itself did not alter GFR or basal rates of cation excretion. A separate group of rats was made tolerant to morphine by subcutaneous implantation of pellets containing 75 mg morphine base. In these rats, AUN also failed to produce any increase in U Na V or U K V by the CK. The results suggest that acute reductions in functioning renal mass produced by either AUN or UUO stimulate cation excretion by the remaining kidney through reflex pathways that involve opiate receptors.
Water removal and solute additions determining increases in renal medullary osmolality
Authors: Schmidt-Nielsen B. , Graves B. , Roth J.
Published: December 2017

Osmolality and solute concentrations of the mammalian renal medulla increase and decrease with changing urine osmolality. These changes are brought about by addition or removal of solute or water to or from the renal medullary tissue. In Munich-Wistar rats and Syrian hamsters, males and females, actual amounts of and the various solutes involved in these changes were determined. Kidneys were removed from animals killed in different stages of water diuresis and antidiuresis. The renal medulla was analyzed by a new method that permits determination of water and solutes on the same piece of tissue. Removal of water and addition of urea were the two most important factors in raising inner medullary osmolality. Papillary water content was inversely related to the papillary osmolality and was 50% lower in extreme antidiuresis compared with water diuresis. Rats had higher papillary water content than hamsters. In the outer medulla, water removal was significant in the hamsters but not in the rats. Addition of urea to the papillary tissue exceeded the osmotic equivalent of NaCl by a factor of 2.8 in both rats and hamsters. Females of both species showed greater changes than males in amounts of urea in the inner medulla.
Barium inhibition of basolateral membrane potassium conductance in tracheal epithelium
Authors: Welsh M. J.
Published: December 2017

Addition of barium ion, Ba2+, to the submucosal bathing solution of canine tracheal epithelium reversibly decreased the short-circuit current and increased transepithelial resistance. The decrease in short-circuit current represented a decrease in the net rate of Cl secretion with no change in the rate of Na absorption. Intracellular microelectrode techniques and an equivalent electrical circuit analysis were used to localize the effect of Ba2+ to an inhibition of the permeability of the basolateral membrane to K. Ba2+ (2 mM) doubled basolateral membrane resistance, decreased the equivalent electromotive force at the basolateral membrane, and decreased the magnitude of the depolarization of basolateral membrane voltage produced by increasing the submucosal K concentration. The inhibition of the basolateral K permeability depolarized the negative intracellular voltage, resulting in both a decrease in the driving force for Cl exit and an estimated increase in intracellular Cl concentration. These studies indicate that there is a Ba2+-inhibitable K conductance at the basolateral membrane of tracheal epithelial cells and that the K permeability plays an important role in the generation of the negative intracellular electrical potential that provides the driving force for Cl exit from the cell.
Furosemide-sensitive Cl transport in embryonic chicken retinal pigment epithelium
Authors: Frambach D. A. , Misfeldt D. S.
Published: December 2017

Retinal pigment epithelium- (RPE) choroid-sclera preparations from embryonic chickens were mounted in an Ussing chamber. A spontaneous transepithelial voltage (Ve) of 5.1 mV (retinal side positive) and a resistance of 114 omega . cm2 can be attributed to the RPE. Furosemide and ouabain inhibited the Ve without affecting the resistance when applied to the retinal surface of the preparation but had no effect when applied to the scleral surface. Acetazolamide and amiloride were without effect when applied to either surface. The Ve fell by 100% in Na-free medium, by 70% in Cl-free medium, and was unchanged in HCO3-free medium. When Na and Cl were returned to the medium, the Ve recovered. Dilution potentials and unidirectional flux studies indicated that the RPE is more permeable to Na than to Cl. Isotope flux studies performed under open-circuit conditions showed a net retina-to-choroid flux for both Na and Cl with the net Cl flux abolished by furosemide. Analysis of the Na+ and Cl- electrochemical gradients and the Na permeability across the RPE suggests that the net retina-to-choroid Na+ flux is largely passive, whereas the net retina-to-choroid Cl- flux results from active transport. These results indicate that embryonic chicken RPE possesses furosemide-sensitive Cl transport function. A model of embryonic chicken RPE transepithelial transport is presented.
Homocellular regulatory mechanisms in sodium-transporting epithelia: avoidance of extinction by flush-through
Authors: Schultz S. G.
Published: December 2017

Page F579: S. G. Schultz. “Homocellular regulatory mechanisms in sodium-transporting epithelia: avoidance of extinction by flush-through.” Page 588: in footnote 5 the paper by Hoffman and Tosteson ( J. Gen. Physiol. 58: 438–466, 1971) was erroneously cited for finding that differences in cation composition between HK and LK sheep erythrocytes are the results of changes in both the Na-K pump and the K leak and the suggestion that the “…molecular mechanism of pump and leak may be closely related.” The correct citation is Tosteson and Hoffman ( J. Gen. Physiol. 44: 169–194, 1960).
Effect of volume expansion and plasma chloride on function of the loop segment
Authors: Booker B. B. , Williams R. H. , Luke R. G.
Published: December 2017

To determine the effect of acute volume expansion and changes in plasma chloride on fluid and chloride uptake in superficial loop segments of rats, this segment was microperfused in vivo at 22 nl/min with a fluid containing Na 145, Cl and 36Cl 130, and HCO3 15 meq/liter during hydropenia and after acute volume expansion with 0.15 M NaCl, 0.15 M NaHCO3, or an isotonic bicarbonate Ringer (Cl 106 meq/liter) solution. Fractional fluid, chloride, and 36Cl reabsorption and early distal chloride concentration did not change during maintained hydropenia (time control) or during volume expansion with NaCl (plasma chloride 120 meq/liter) or bicarbonate Ringer solution (plasma chloride 104 meq/liter). Absolute and fractional reabsorption of chloride and 36Cl increased, without change in fluid reabsorption, and early distal chloride diminished after infusion of NaHCO3 (plasma chloride 90 meq/liter). It is concluded that acute volume expansion, per se, has no effect on either net fluid or net chloride absorption in the superficial loop segment at the load studied. Hypochloremia is associated with increased net reabsorption of chloride and an increased unidirectional efflux of chloride from the loop segment during acute volume expansion, most likely due to a gradient effect on the thick ascending limb of the loop of Henle.
Intracellular Cl- activity of the proximal tubule of Triturus kidney: dependence on extracellular ionic composition and transmembrane potential
Authors: Yoshitomi K. , Hoshi T.
Published: December 2017

Intracellular Cl- activity (aiCl) was measured with double-barreled Cl- -selective microelectrodes in Triturus proximal tubule and the effects of ionic composition of the perfusion solutions and the cell membrane potentials were studied. In the absence of HCO-/3, aiCl averaged 22.4 +/- 0.4 mM, the value being 3.8 times that expected from the Nernst equation. Increases in peritubular HCO -/3 concentration without changing pH resulted in drastic decreases in aiCl. Addition of HCO-/3 to only the luminal fluid had no effect. Elimination of Na+ from the luminal fluid caused no immediate changes in aiCl, but long-lasting perfusions with a Na+-free solution resulted in a gradual decrease in aiCl. Lowering or raising intraluminal pH rapidly increased or decreased aiCl, respectively. Alanine-induced depolarization of the cell membranes exceeding 15-20 mV rapidly increased aiCl, and the increase was proportional to the driving force for Cl-. The results suggest the presence of a Cl-/OH- antiport mechanism in the luminal membrane and a Cl-/HCO-/3 exchange mechanism and voltage-dependent rectifying Cl- pathways in the peritubular membrane.
Sodium-dependent succinate transport in renal outer cortical brush border membrane vesicles
Authors: Fukuhara Y. , Turner R. J.
Published: December 2017

The transport of succinate into outer cortical brush border membrane vesicles (early proximal tubule) was studied. Succinate is taken up into an osmotically active space and exhibits the same distribution volume and the same degree of nonspecific binding and trapping as D-glucose. Succinate uptake is markedly enhanced by sodium and slightly enhanced by lithium but shows no stimulation by other monovalent cations tested. Kinetic analysis of the sodium-dependent component of succinate flux indicates a single transport site obeying Michaelis-Menten kinetics (Km = 1 mM and Vmax = 50 nmol X min -1 X mg protein -1 as measured under zero trans conditions at 100 mM NaCl and 28 degrees C with delta psi = 0). Direct evidence is given that succinate transport is coupled to sodium and is rheogenic, involving the net transfer of positive charge. The sodium:succinate coupling stoichiometry is found to be 2:1 by two independent methods.
Development of solute transport in rabbit proximal tubule. II. Morphologic segmentation
Authors: Evan A. P. , Gattone V. H. , Schwartz G. J.
Published: December 2017

We examined the segmental morphologic maturation of the proximal tubule in order to identify some of the factors influencing the development of solute transport. Proximal tubules from the outer, middle, and inner kidney cortex were obtained from rabbits during the entire period of development and studied using transmission and scanning electron microscopy, microdissection, and semiquantitative morphometric analysis. The location of the tubule in the cortex was established by identifying its own glomerulus. The 1-wk-old rabbit showed the most immature proximal tubules in the outer cortex and a gradation of more mature tubules toward the inner zone. Only the inner cortical tubules were segmented at this time. The outer cortical tubules showed limited development for the 1st 2-3 wk after birth, while the inner cortical tubules were morphologically mature by 3-4 postnatal wk. Morphometric analysis revealed that the areas of apical, basolateral, and mitochondrial membranes developed at similar rates. Clearly, morphologic maturation of proximal tubules was reached at different times depending on the cortical origin. We conclude that a serial developmental examination of transport in proximal tubules should require the careful identification of the origin of each tubule in the cortex; otherwise, time-dependent comparisons will be complicated by the inclusion of nephrons of diverse postnatal ages. In practice, at this time, the use of proximal tubules from the inner cortex throughout development, or from the outer cortex beyond 2-3 wk of age, permits such serial measurements and comparisons in the rabbit.
Determination of postglomerular permselectivity to neutral dextrans in the dog
Authors: Whiteside C. , Silverman M.
Published: December 2017

The single-pass multiple-indicator-dilution (MID) technique was used to analyze postglomerular capillary permeability. Anesthetized mongrel dogs (n = 13) during mannitol diuresis received a pulse injection of 125I-albumin (plasma reference), [14C]inulin (glomerular reference), creatinine (interstitial reference), and a homogeneous [3H]dextran molecular weight marker 6,000-12,000 dalton in the left renal artery. Simultaneous left renal venous outflow and right and left urine were rapidly sampled. Left urine recoveries of creatinine, [14C]inulin, and [3H]dextran were identical, indicating no glomerular solute flux limitation. Progressive precession of the [14C]inulin and [3H]dextran renal vein curves relative to creatinine indicated increasing postglomerular limitation to solute flux proportional to molecular size. The postglomerular solute extraction (EPG) (renal vein upslope indicator/125I-albumin) varied inversely with postglomerular renal plasma flow (F), indicating diffusion limitation. Ouabain infusion into the left renal artery significantly reduced Na reabsorption but did not alter the EPG of [14C]inulin or [3H]dextran. Permeability-surface (PS) area products calculated from EPG and F ranged from 4.86 +/- 0.89 to 0.97 +/- 0.25 (SD) cm X s-1 X 100 g-1 for indicators 5,000-12,000 dalton. [14C]Inulin PS products remained constant for F greater than or equal to 2.50 ml X s-1 X 100 g kidney-1. PS[3H]dextran/PS[14C]In (n = 20, F greater than or equal to 2.5 ml X s-1) was used to calculate an effective postglomerular capillary pore radius, r = 55.5 +/- 7.6 (SD) A.
Application of the disequilibrium pH method to investigate the mechanism of urinary acidification
Authors: DuBose T. D.
Published: December 2017

DuBose, Thomas D., Jr. Application of the disequilibrium pH method to investigate the mechanism of urinary acidification. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F535-F544, 1983.--The cellular mechanism of renal bicarbonate reabsorption has been debated for four decades. Recent technological advances have allowed distinction between primary bicarbonate reabsorption and a proton secretory mechanism. The disequilibrium pH method has been applied widely for this purpose and has supported the latter hypothesis uniformly. The demonstration of elevated values for PCO2 in tubular and vascular structures of the renal cortex has not altered this view. Indeed, by employing a newly developed method for measurement of equilibrium pH in vivo that permits contact with the environment within the tubule lumen to continue, we demonstrated an acid disequilibrium pH in the proximal tubule after carbonic anhydrase inhibition equal to -0.68 pH units. A spontaneous disequilibrium pH was not present in the distal tubule during control conditions or during metabolic alkalosis but was demonstrated during combined respiratory acidosis-metabolic alkalosis. This finding agrees qualitatively with observed rates of bicarbonate reabsorption in the perfused distal tubule in vivo. With use of similar techniques, an acid disequilibrium pH in conjunction with elevated values for PCO2 was observed in the papillary collecting duct. Thus, proton secretion appears to be the predominant mechanism of bicarbonate reabsorption in superficial nephrons and explains, as well, the means by which the urine-to-blood PCO2 gradient in alkaline urine is established.
Aldosterone binding in isolated tubules. III. Autoradiography along the rat nephron
Authors: Farman N. , Bonvalet J. P.
Published: December 2017

Aldosterone binding was investigated along the nephron of adrenalectomized Wistar rats. Autoradiographs of microdissected tubular segments were performed on dry film after incubation with [3H]aldosterone [( 3H]A) at 2 X 10(-10), 2 X 10(-9), and 2 X 10(-8) M in the presence or absence of an excess unlabeled hormone. Competition studies were done with a 10 times excess A, dexamethasone (D), and estradiol in the presence of 2 X 10(-8) [3H]A. Specific nuclear labeling predominated in the cortical collecting tubule (CCT) and A specificity of the binding was assessed by the much better displacing potency of unlabeled A as compared with D. Labeling in the distal tubule (DCT) resembled that of CCT, but D was nearly as good a competitor as A. In the loop and medullary collecting tubule, labeling was lower, with mixed steroid specificity. No specific nuclear labeling was detectable in the proximal tubule. We conclude that the CCT and DCT present the highest binding capacity for aldosterone. Competition studies revealed that the CCT is probably the more specific mineralocorticoid target segment. In other segments beyond the pars recta (loop of Henle, medullary collecting tubule), aldosterone probably binds to both mineralocorticoid and glucocorticoid binding sites. No major difference appeared between the profile of aldosterone binding along the rat tubule and the one previously described in the rabbit.
Journals in the eighties
Authors: Morgan H. E. , Farhi L. E. , Windhager E. E.
Published: December 2017

Acknowledgments from the Publications Committee.
Pi transport, phosphorylation, and dephosphorylation in renal membranes from HYP/Y mice
Authors: Hammerman M. R. , Chase L. R.
Published: December 2017

To ascertain whether cAMP-dependent phosphorylation could be demonstrated in brush border membrane vesicles (BBMV) isolated from kidneys of mice with X-linked hypophosphatemic rickets (HYP/Y) and normal littermates (+/Y) and, if so, to determine whether the absence of dephosphorylation might underlie differences in Na+-dependent 32Pi transport in BBMV, we measured 1) 32Pi transport, 2) cAMP-dependent phosphorylation, and 3) dephosphorylation in BBMV from +/Y and HYP/Y mice. Na+ gradient-dependent 32Pi transport was decreased in BBMV from HYP/Y mice as reflected in a decreased apparent Vmax. cAMP-dependent phosphorylation of a 62,000 Mr protein was demonstrated in sodium dodecyl sulfate polyacrylamide gels of BBMV from +/Y and HYP/Y mice and was associated with decreased Na+-dependent 32Pi transport. Dephosphorylation of the 62,000 Mr band was demonstrable in both types of membranes. Thus, both cAMP-dependent protein kinase and phosphoprotein phosphatase activities were demonstrable in BBMV isolated from +/Y and HYP/Y mice. These results are consistent with the renal tubular defect in the HYP/Y mouse reflecting an intrinsic abnormality of Pi transport in the brush border membrane independent from mediation of the phosphaturic effect of parathyroid hormone.