bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in cardiovascular and renal function during catecholamine infusions in developing swine
Authors: Buckley N. M. , Charney A. N. , Brazeau P. , Cabili S. , Frasier I. D.
Published: December 2017

Renal and cardiac effects of norepinephrine and dopamine were evaluated in swine aged 1 wk, 2 wk, and 6 mo. The swine were anesthetized with pentobarbital (20-30 mg/kg). Aortic pressure, right ventricular pressure and its first derivative, and heart rate were recorded, together with carotid and renal (RBF) arterial flows. Glomerular filtration rate (GFR) was determined by [14C]inulin clearance. After a control period, norepinephrine or dopamine was infused intravenously for 10-20 min before and then during another clearance period. After a second control period, the second catecholamine was infused. GFR increased in piglets given either catecholamine. Norepinephrine at equipressor doses (2.0 micrograms.kg-1.min-1 in piglets and 1.0 micrograms.kg-1.min-1 in mature swine) decreased RBF and increased renal resistance. Dopamine at equi-inotropic doses (10 micrograms.kg-1 min-1 in piglets and 20 micrograms.kg-1.min-1 in mature swine) increased RBF and decreased renal resistance only in mature swine. Infusions of dopamine at a low dose (5 micrograms.kg-1.min-1) also failed to increase RBF or decrease renal resistance in piglets. The results suggest that maturation of the mechanism of renal vasodilation by dopamine occurs later than that for vasoconstriction by norepinephrine.
Oxalate secretion in the rat proximal tubule
Authors: Knight T. F. , Sansom S. C. , Senekjian H. O. , Weinman E. J.
Published: December 2017

Simultaneous capillary and luminal microperfusion studies in the proximal convoluted tubule of the rat were performed to examine the transepithelial secretory flux of [14C]oxalate. Increases in the concentration of oxalate in the capillary solution from 0.096 to 4.3 mM resulted in progressively higher rates of oxalate secretion into the lumen. Further increases in the capillary concentration of oxalate indicated a tendency toward a plateau. The inclusion of para-chloromercuribenzoate, sodium cyanide, indanyloxyacetic acid, furosemide, or para-aminohippurate in the capillary solution significantly lowered the secretory flux of oxalate. the addition of probenecid in a concentration of 10(-4) M inhibited oxalate secretion when the oxalate concentration in the capillary solution ranged between 1.1 and 4.3 mM, but did not affect oxalate secretion at higher capillary concentrations of oxalate. These results indicate that oxalate secretion in the rat proximal tubule is an active carrier-mediated process. When considered in conjunction with prior studies, the present investigations suggest the possibility that more than one oxalate secretory system exists in the rat proximal tubule.
Renal and systemic acid-base effects of chronic spironolactone administration
Authors: Hulter H. N. , Bonner E. L. , Glynn R. D. , Sebastian A.
Published: December 2017

Studies in dogs were carried out to investigate the effects of chronic administration of the mineralcorticoid antagonist spironolactone (15 mg/kg orally) on renal and systemic acid-base metabolism. In adrenalectomized dogs administered fixed mineralocorticoid and glucocorticoid replacement, spironolactone resulted in a definite renal antimineralocorticoid effect, as evidenced by natriuresis and chloruresis, and sustained metabolic acidosis and hyperkalemia due in part to impaired renal secretion of hydrogen and potassium. In adrenalectomized dogs receiving physiological glucocorticoid without mineralocorticoid, metabolic acidosis also occurred, but a marked stimulatory effect of spironolactone on net acid excretion occurred in association with increased urinary SO4-2 and total nitrogen excretion. Accordingly, spironolactone results in sustained renal tubular acidosis when administered in the presence of constant physiological levels of mineralocorticoid and glucocorticoid steroids. When administered under conditions of complete lack of mineralocorticoid activity, spironolactone exerts systemic and renal acid-base effects similar to those of a glucocorticoid steroid, namely, increased protein catabolism and sulfuric acid production with resultant extrarenal metabolic acidosis associated with increased net acid excretion.
Role of deep nephrons and the terminal collecting duct in a mannitol-induced diuresis
Authors: Buerkert J. , Martin D. , Prasad J. , Trigg D.
Published: December 2017

Recollection micropuncture in Munich-Wistar rats was used to study the effects of intravenous hypertonic mannitol infusions on fluid reabsorption by surface nephrons, prior to the bend of Henle's loop of deep nephrons, and along the papillary collecting duct. During mannitol diuresis, single nephron glomerular filtration rate rose significantly in surface nephrons but fell in deep nephrons. Although mannitol increased the delivery of sodium and water to the end of the proximal tubule and to the first portion of the distal tubule of surface nephrons, water and sodium were reabsorbed between these two sites. In deep nephrons, water reabsorption prior to the bend of the loop of Henle was significantly decreased. Absolute sodium delivery to this site was reduced despite a marked decrease in fractional sodium reabsorption prior to the bend. Papillary osmolality was decreased. Renal plasma flow and inner medullary plasma flow (IMPF) increased proportionally. The reduced water extraction prior to the bend of deep nephrons and the decrease in papillary osmolality could have been partly due to a concomitant increase in IMPF and a decrease in sodium delivery to the medulla. The reabsorption of delivered sodium and water by the papillary collecting duct was reduced to a greater extent than could be expected from the increase in sodium delivery.
Distribution of hexokinase and phosphoenolpyruvate carboxykinase along the rabbit nephron
Authors: Vandewalle A. , Wirthensohn G. , Heidrich H. G. , Guder W. G.
Published: December 2017

Radiochemical microprocedures were developed for the determination of hexokinase and phosphoenolpyruvate carboxykinase (PEPCK) activity in single microdissected segments of the mature rabbit nephron dissected from fresh tissue after collagenase treatment. All results were related to tubular length and tubular protein content. Hexokinase activity was found to be lowest in the proximal convoluted tubule and to increase along the following nephron segments, with highest activity in the connecting tubule. The gluconeogenic enzyme PEPCK, on the other hand, was exclusively found in the proximal tubule. Early and late portions of the convoluted segment exhibited the same specific activity, but only 50% was found in the pars recta. All other renal structures exhibited only insignificant activity of PEPCK. The results show that renal glucose metabolism and gluconeogenesis are clearly separated. As previously shown for the cytosolic rat enzyme, rabbit mitochondrial PEPCK is also exclusively a proximal tubular enzyme, thus confirming the dominant role of this segment in mammalian renal gluconeogenesis. The high activity of hexokinase in the segments of the distal tubule points to the role of glucose as metabolic fuel, glycogen precursor, and other glucose-6-phosphate-using pathways in these structures.
Release of PGE and PGI2 in the pump-perfused dog kidney and associated hypotension
Authors: Wong P. C. , Zimmerman B. G. , Friedman P.
Published: December 2017

The mechanism of enhanced renal prostaglandin (PG) release in the in situ pump-perfused kidney was studied in anesthetized dogs. Pump perfusion caused a gradual decrease in mean arterial blood pressure (BP) from 163 to 128 mmHg over an 80-min period. The renal arteriovenous level of PGE and plasma renin activity (PRA) were increased by a mean of 1.36 ng/ml and 22 ng AI.ml-1.h-1, respectively. In a second group of dogs treated with captopril, pump perfusion did not alter PGE or BP, but increased PRA. When the animals were treated with indomethacin, the renal arteriovenous levels of PGE and 6-keto-PGF1 alpha were not changed but PRA increased during the 80 min of pump perfusion. In a fourth group of dogs that had undergone renal denervation and phentolamine treatment, changes in PGE and BP occurred during pump perfusion similar to the changes in the control group, and 6-keto-PGF1 alpha release by the kidney also increased. The results indicate that renal PG release during group perfusion is mainly due to the activation of the renin-angiotensin system and that the hypotension due to pump perfusion is PG mediated.
Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture
Authors: Grenier F. C. , Rollins T. E. , Smith W. L.
Published: December 2017

Cells having morphological and histochemical properties of collecting tubules were isolated from rabbit renal papillae. Confluent monolayer cultures of these renal papillary collecting tubule (RPCT) cells formed hemicysts and adhered with morphological asymmetry to Millipore filters. Cultures of 1-day-old RPCT cells synthesized cAMP in response to arginine vasopressin (AVP) (half-maximal response to 10(-10) M), oxytocin, and parathyroid hormone (half-maximal responses at 5 X 10(-9) M) but not to adrenergic agents. After 10 days of growth (fourfold increase in cell number) RPCT cells retained the same pattern of histochemical and hormonal responses as 1-day-old cells. Hormones were tested for their influence on the release of immunoreactive prostaglandins (iPG) by RPCT cells; the major product under both basal and stimulated conditions was iPGE2. At very low concentrations (greater than or equal to 10(-10) M), bradykinin, lysyl-bradykinin, and methionyl-lysyl-bradykinin caused four- to sixfold increases in the rate of iPGE2 formation within 3 min; smaller (less than twofold) increases were observed with relatively high concentrations of epinephrine (10(-5) M), norepinephrine (10(-5) M), and angiotensin II (10(-7) M), but only after longer incubations. Significantly, neither AVP (10(-7) M) nor [deamino]AVP (10(-7) M) caused prostaglandin release by RPCT cells. Our results indicate that kinins can act directly on the collecting tubule to elicit PGE2 formation; furthermore, this effect of kinins may be natriuretic, since PGE2 has been shown to inhibit Na+ resorption by the medullary collecting tubule and thick ascending limb.
Regulation of renal Na+-K+-ATPase in the rat by adrenal steroids
Authors: Rodriguez H. J. , Sinha S. K. , Starling J. , Klahr S.
Published: December 2017

The effects of single and multiple injections of aldosterone and dexamethasone on renal Na+-K+-ATPase, in vitro renal gluconeogenesis, and urinary electrolyte excretion were examined in adrenalectomized rats in a dose-dependent manner. Single maximal and supramaximal doses of aldosterone (defined by the effect of electrolyte excretion) had no effect on Na+-K+-ATPase or gluconeogenesis. By contrast, a single administration of dexamethasone (in a dose range that increased fasting blood sugar, stimulated renal gluconeogenesis, and had no mineralocorticoid effects) yielded clear-cut activation of Na+-K+-ATPase. Multiple submaximal doses of dexamethasone produced quantitatively similar stimulation of Na+-K+-ATPase and gluconeogenesis. Multiple supramaximal doses of aldosterone stimulated Na+-K+-ATPase and gluconeogenesis, but maximal and submaximal doses of the hormone were without effect. Aldosterone had no effect on hepatic Na+-K+-ATPase or gluconeogenesis. These results suggest that activation of renal Na+-K+-ATPase can be considered a putative glucocorticoid (not mineralocorticoid) effect. Renal Na+-K+-ATPase activation by chronic aldosterone treatment may be mediated by glucocorticoid receptor sites and, hence, may not represent a genuine mineralocorticoid effect.
Vasopressin, theophylline, PGE2, and indomethacin on active Na transport in frog skin: studies with microelectrodes
Authors: Els W. J. , Helman S. I.
Published: December 2017

Active transepithelial Na transport in frog skin is influenced by vasopressin, theophylline, indomethacin, and PGE2. During stimulation or inhibition of the short-circuit current, the transapical membrane voltage of short-circuited skins was recorded using an intracellular microelectrode. The microelectrode also permitted determination of the fractional resistance of the apical barrier of the cells (fRo) and the E'1 (transepithelial voltage at which the apical membrane voltage is zero). Analysis of the data according to an electrical model proposed previously indicated that changes of ISC were mediated primarily via changes of the slope resistance Rfo (Vo negative) of the apical barrier of the cells with little or no effect on the Thevenin emf or resistance of the basolateral membranes. These data are in accordance with previous observations that ADH had no effect on the ENa and are discussed in relation to the origin of the ENa at the basolateral membranes of the epithelial cells.
Potassium absorptive pump at the luminal membrane of turtle urinary bladder
Authors: Husted R. F. , Steinmetz P. R.
Published: December 2017

In the absence of transepithelial electrochemical gradients, the direction of net K transport across the turtle urinary bladder is from the mucosal (M) to the serosal (S) solution. Under control conditions, M leads to S flux was 101 +/- 5 nmol . h-1 . (8 cm2)-1, S leads to M flux was 59 +/- 4, and the net absorptive flux was 42 +/- 6. The K absorptive pump was characterized by examining its dependence on voltage and ambient sodium and its sensitivity to mucosal ouabain. Lumen-negative voltages caused an increase rather than the expected decrease in active K absorption. Thus, the active K flux appeared to be coupled to a flow of positive charge in the opposite direction, possibly representing Na secretion in excess of K absorption. Net K absorption was abolished by removal of Na from the medium and by mucosal, but not serosal, addition of ouabain. The reverse electrogenicity, Na dependence, and ouabain sensitivity of K absorption indicate that the K pump of the mucosal membrane has characteristics of a Na-K-ATPase.
ADH-PGE2 interactions in cortical collecting tubule. I. Depression of sodium transport
Authors: Holt W. F. , Lechene C.
Published: December 2017

Antidiuretic hormone (ADH) (200 microunits/ml Pitressin or synthetic arginine vasopressin) causes a transitory increase followed by a sustained decrease in the potential difference (PD) and in the net fluxes of sodium and chloride across rabbit cortical collecting tubules perfused in vitro. The inhibitory action of vasopressin is reversible; removal of the hormone from the bath promotes recovery in the PD and in the transport of sodium and chloride to the level of the controls. After 70 min of incubation with ADH, 10(-5) M meclofenamate, an inhibitor of the synthesis of prostaglandins, was added to the bath of some tubules. Despite the presence of ADH, the PD and ionic fluxes increased to control levels. The introduction of exogenous prostaglandin E2 (10(-5) M PGE2) to the bathing medium containing ADH and meclofenamate mimicked the inhibitory action of ADH, decreasing the PD and the reabsorption of sodium and chloride. Pretreatment of collecting tubules with meclofenamate prevented the inhibitory effect of ADH. These findings show that vasopressin exerts a prolonged inhibitory action on PD and on net reabsorption of Na and Cl and that this action may be exerted through stimulating the biosynthesis of prostaglandin E2 by the cortical collecting tubule.
ADH-PGE2 interactions in cortical collecting tubule. II. inhibition of Ca and P reabsorption
Authors: Holt W. F. , Lechene C.
Published: December 2017

In the absence of ADH, microperfused cortical collecting tubules of rabbits reabsorb calcium and phosphorus. Antidiuretic hormone (ADH) (200 microunits/ml Pitressin or synthetic arginine vasopressin) inhibits the reabsorption and may promote the secretion of calcium and phosphorus. At 5 min after incubation with ADH, there was a transitory increase in the potential difference and the reabsorption of sodium. The fluxes of calcium and phosphorus, however, showed no significant change from the control values. At 30-50 min after treatment with ADH, the reabsorption of calcium and phosphorus was inhibited and in some tubules calcium and phosphorus were secreted. The removal of vasopressin from the bath or the addition of 10(-5) M meclofenamate in vitro prevented ADH from inhibiting the reabsorption of calcium and phosphorus. Treatment of tubules with 10(-5) M prostaglandin E2 (PGE2) subsequent to incubation in a medium containing ADH and meclofenamate inhibited the reabsorption or even promoted the secretin of calcium and phosphorus, as did the prolonged incubation with ADH alone. We conclude that cortical collecting tubules reabsorb calcium and phosphorus in the absence of vasopressin and that ADH inhibits calcium and phosphorus reabsorption. Endogenous synthesis of PGE2 may mediate the inhibitory action of ADH, since meclofenamate (an inhibitor of the synthesis of prostaglandins) opposes and exogenous PGE2 mimics ADH.
Active transport of Rb+ across skin of the teleost Gillichthys mirabilis
Authors: Marshall W. S.
Published: December 2017

The fluxes of 86Rb were measured across the isolated skin of the marine teleost Gillichthys. The efflux of 86Rb in Cl Ringer with 1.0 mM RbCl exceeded the influx by 8.0 +/- 1.2 neq . cm-2 . h-1 at closed circuit, indicating active transport of Rb+ in the secretory direction. However, the net Rb+ flux was not significantly different from zero in (Cl-free) gluconate Ringer, indicating that the active Rb+ transport was Cl dependent. The epithelium behaved as a single passive resistor to Rb+ in the absence of Cl-, and Rb+ movement under these conditions appeared to be by Fickean diffusion. Epinephrine (10(-5) M) inhibited partially the active Rb+ transport in Cl Ringer. These results suggest that there is active K+ transport across Gillichthys skin.
Renal handling of zinc: effect of cysteine infusion
Authors: Abu-Hamdan D. K. , Migdal S. D. , Whitehouse R. , Rabbani P. , Prasad A. S. , McDonald F. D.
Published: December 2017

Zinc clearance studies in anesthetized dogs were performed during hydropenia, mannitol infusion, and infusion of mannitol plus ZnSO4, ZnCL2, or cysteine. Mannitol expansion caused no significant change in Zn clearance. ZnSO4 infusion increased filtered Zn 13-fold without changing clearance. Zn excretion increased only sixfold, indicating increased net Zn reabsorption. Cysteine infusion increased urinary Zn excretion 86-fold, indicating net tubular Zn secretion, some of which derived from nonplasma sources. Stop-flow studies localized Zn reabsorption to the distal nephron during infusion of mannitol and mannitol plus ZnSO4 or ZnCl2. Net Zn secretion was shown to occur in the proximal tubule during cysteine infusion with reversal of the distal reabsorption pattern seen during ZnSO4 and ZnCl2 infusion. Despite increased urinary Zn excretion during ZnSO4 infusion, calcium excretion was unaltered. During cysteine infusion dissociation of tubular handling of CA2+ and Zn occurred in both the proximal and distal tubule. These experiments demonstrate that the nephron under these experimental conditions is capable of both proximal secretion and distal reabsorption of Zn.
Altered PGE2 and PGF2 alpha production by glomeruli and papilla of sodium-depleted and sodium-loaded rats
Authors: Chaumet-Riffaud P. , Oudinet J. P. , Sraer J. , Lajotte C. , Ardaillou R.
Published: December 2017

Prostaglandin (PG) E2 and F2 alpha synthesis by isolated glomeruli and papillary homogenates prepared from control, salt-loaded, and salt-depleted rats was measured in vitro with and without added arachidonic acid using specific radioimmunoassays. Glomeruli from salt-depleted rats synthesized less PGE2 and more PGF2 alpha than glomeruli from control rats under both conditions. The effect of sodium restriction could be attributed to stimulation of glomerular 9-keto-PGE2 reductase activity unrelated to a change in the concentration of this enzyme. High salt diet had no effect on PG synthesis by glomeruli. Papillary homogenates prepared from salt-loaded rats synthesized more PGE2 than those from control rats both with and without added arachidonic acid. This finding suggests an effect of high salt diet at a stage further than phospholipid deacylation. Low salt diet had no effect on PG synthesis by papillary homogenates. The physiological control of PG synthesis in response to changes in the NaCl content of the diet is, therefore, different for the glomeruli and the papilla.
Uptake of [3H]PAH and [14C]urate into isolated proximal tubular segments of the pig kidney
Authors: Schali C. , Roch-Ramel F.
Published: December 2017

Segments of proximal convoluted (PCT) and proximal straight (PST) tubules of minipigs and normal-sized pigs were microdissected (without collagenase treatment) and incubated (30 min, 37 degrees C, pH 7.4) in Ringer solution (under O2) containing [3H]PAH (3.10(-5) M) or [14C]urate (9.10(-5) M) and, in inhibitor studies, probenecid, pyrazinoic acid (PZA), urate or PAH, all at 1 mM. In both strains the uptake of [3H]PAH expressed as means T/M ratio (cpm per ml tissue water/cpm per ml incubation medium) was significantly higher (P less than 0.001) in PCT than in PST. T/M was 34.7 +/- 5.6 (SE) in 34 PCT and 2.4 +/- 0.3 in 24 PST of eight minipigs. In two normal-sized pigs the T/M was 14.1 +/- 3.6 in 15 PCT and 1.4 +/- 0.1 in six PST. Similar results were obtained for [14C]urate. In eight minipigs the T/M was 4.9 +/– 0.5 in 24 PCT and 2 +/- 0.2 in 25 PST. In normal-sized pigs the T/M was 3.8 +/- 0.3 in 35 PCT (five pigs) and 1.9 +/- 0.4 in eight PST (two pigs). In inhibitor studies urate significantly depressed the uptake of [3H]PAH, and unlabeled PAH depressed the uptake of [14C]urate. PZA significantly inhibited the uptake of [14C]urate but not that of [3H]PAH, whereas probenecid had a strong inhibitory effect on the uptake of both compounds. These results suggest that [14C]urate and [3H]PAH are transported by a transport system located mainly in the proximal convoluted tubule. These findings are in contrast to the findings obtained in rabbits in which the transport system of PAH and urate is mainly located in the proximal part of the pars recta.
Effects of chloride substitutes on PAH transport by isolated perfused renal tubules
Authors: Dantzler W. H. , Bentley S. K.
Published: December 2017

Effects of substituting isethionate, methyl sulfate, or thiocyanate for chloride on p-aminohippurate (PAH) transport by isolated perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. In the perfusate, isethionate or methyl sulfate substitution irreversibly depressed net PAH secretion and the apparent PAH permeability of the luminal membrane by about 60–80%, whereas thiocyanate substitution had no effect. In the bathing medium, isethionate substitution reversibly stimulated net PAH secretion by about 35% without changing the apparent permeability of the peritubular membrane to PAH (Pp); thiocyanate substitution reversibly inhibited net PAH secretion by about 45% without affecting Pp; and methyl sulfate substitution had no effect. With simultaneous substitutions in perfusate and bath, isethionate depressed net PAH secretion irreversibly, whereas thiocyanate had no effect. Effects on PAH transport were not simply the result of changes in transepithelial potential or of the changes in net transepithelial fluid movement. These data strengthen the concept that net PAH secretion involves different mediated steps at the peritubular and luminal membranes. Since these tubules are highly permeable to thiocyanate and poorly permeable to isethionate and methyl sulfate, the data suggest that the mediated step from cells to lumen does not require chloride in the lumen but does require a highly permeant anion.
Effects of vasopressin and urea on Ca2+-calmodulin-dependent renal prostaglandin E
Authors: Craven P. A. , DeRubertis F. R.
Published: December 2017

Vasopressin (AVP stimulated immunoreactive E (iPGE) synthesis and the release of [3H]arachidonate (AA) from prelabeled slices of rat inner medulla (IM) in the presence but not in the absence of Ca2+ (plus 2 mM EGTA). Urea (700–1,200 mosM) inhibited these actions. By contrast Ca2+ deprivation or urea did not suppress AVP-induced increases in cAMP or stimulation of iPGE by exogenous AA. At 10–50 microM, trifluoperazine (TFP) suppressed AVP-induced increases in [3H]AA release and iPGE accumulation, but not increases in cAMP. Basal acyl hydrolase activity (AH) of 2,000 g particulate fractions of IM was suppressed by EGTA. Ca2+, but not Mg2+ or AVP, restored AH to levels observed in the absence of EGTA. Ca2+-induced increases in particulate AH were inhibited by urea (700–1,200 mosM) or TFP (10–50 microM), but not 1,000 mosM NaCl. Partial depletion of particulate calmodulin-like activity suppressed Ca2+-induced increases in AH. The latter was restored with 1 microM purified exogenous calmodulin but not troponin C. The results demonstrate that AVP stimulation of AA and PGE release in IM are Ca2+-dependent processes suppressed by urea. They also suggest a role for Ca2+-calmodulin-dependent AH in the control of PG synthesis in IM.
Methodologic considerations in the study of glomerular ultrafiltration
Authors: Osgood R. W. , Reineck H. J. , Stein J. H.
Published: December 2017

Over the past decade numerous studies have detailed the dynamics of glomerular ultrafiltration. Observations in a unique strain of Munich-Wistar rats, which afford the direct measurement of intraglomerular capillary hydrostatic pressure, have determined that under normal physiologic conditions these animals are in a state of filtration equilibrium. Both mathematical models based on this observation and experimental evidence indicate that under these circumstances the primary determinant of glomerular filtration rate (GFR) is the rate of glomerular plasma flow. In addition, this state of filtration equilibrium provides a condition in which changes in the product of glomerular surface area and glomerular capillary hydraulic conductivity (ultrafiltration coefficient) have no influence on glomerular filtration rate. Similarly, changes in glomerular hydrostatic pressure have a relatively small influence on GFR. These conclusions represent a marked alteration of the previously held concepts of the determinants of GFR. Unfortunately, studies in other strains of rats and in other animal species, particularly the dog, have led to the conclusion that filtration disequilibrium is the normal physiologic condition. The validity of this conclusion, however, is made uncertain by methodologic necessities that may lead to erroneous physiologic measurements of the determinants of GFR. In the present Editorial Review we examine the data reflecting on the applicability of filtration equilibrium to mammalian species. In addition, we summarize two new in vitro techniques for the further study of the dynamics of glomerular ultrafiltration.
Coulometric acid-base titration in nanoliter samples with glass and antimony electrodes
Authors: Karlmark B. , Jaeger P. , Fein H. , Giebisch G.
Published: December 2017

A modification of the coulometric acid-base titration method is described for the measurement of titratable acid and ammonium in nanoliter samples. The main components consist of a pH-seeking device and a miniaturized antimony electrode system capable of delivering OH- ions at a known rate. The modifications include use of a cup-shaped pH-sensitive glass-membrane electrode for monitoring pH changes during titration and a new electronic titration circuit consisting of a high-impedance differential electrometer, a constant-current source, and an electronic integrating circuit. Details regarding the construction of the components of the titration system and practical aspects of its use are also provided.
Inhibition of ADH-stimulated water flow by stable prostaglandin endoperoxide analogues
Authors: Ludens J. H. , Taylor C. J.
Published: December 2017

The synthetic prostaglandin endoperoxide analogues 15-hydroxy-9,11-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-I) and 15-hydroxy-11,9-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-II) inhibited ADH-induced water flow in the isolated urinary bladder of the toad. In certain other biologic systems, EPA-I appeared to possess "thromboxane-like" activity. Thromboxanes, therefore, as well as the classical E prostaglandins may be modulators of the ADH response. To further characterize the effect of EPA-I on ADH, interaction studies were conducted with a related endoperoxide analogue found to be devoid of anti-ADH activity, 9,11-(epoxymethano)prostan-1-oic acid (EPA-III), and a prostanoid found to be a PGE antagonist in isolated toad bladder, 7-oxa-13-prostynoic acid. EPA-III reversed the anti-ADH activity of EPA-I but not that of PGE2. In contrast, 7-oxa-13-prostynoic acid reversed the anti-ADH activity of PGE2 but not that of an equieffective concentration of EPA-I. These findings suggest that the anti-ADH activity of EPA-I, and by inference thromboxane A2, may be mediated via a different receptor and/or pathway than that of the E prostaglandins.
Conditions for enhancement of renin release by isoproterenol, dopamine, and glucagon
Authors: Holdaas H. , Langaard O. , Eide I. , Kiil F.
Published: December 2017

Isoproterenol infusion increases renin release at low but not at control blood pressure. To examine whether this effect is dependent on arteriolar dilation and is specific for agonists of beta-adrenoceptors, responses to intrarenal infusion of isoproterenol (0.2 micrograms.kg body wt-1.min-1), glucagon (0.1 micrograms.kg body wt-1.min-1), and dopamine (1 micrograms.kg body wt-1.min-1) were compared at control and low or high ureteral pressure, which also dilates the renal arterioles. During renal arterial constriction, renin release was equal at two perfusion pressures below the range of autoregulation and was 76 +/- 24 micrograms/min higher during isoproterenol than during propranolol administration. Intravenous infusion of isoproterenol gave qualitatively similar results. Intrarenal infusion of glucagon and dopamine increased renin release by 13 +/- 3 and 22 +/- 12 micrograms/min, respectively; enhancement of renin release was also present after propranolol administration. During ureteral occlusion, intrarenal infusion of isoproterenol, dopamine, and glucagon increased renin release from 30-40 micrograms/min by 78 +/- 11, 13 +/- 3, and 31 +/- 10 micrograms/min, respectively. At control blood and ureteral pressure, the effects on renin release of infusing isoproterenol, dopamine, or glucagon were small or absent. Thus, isoproterenol, dopamine, amd glucagon enhance renin release when the arterioles are dilated by renal arterial constriction or ureteral occlusion.
New pathways for potassium transport in the kidney
Authors: Jamison R. L. , Work J. , Schafer J. A.
Published: December 2017

This review focuses on the hypothesis that potassium is recycled in the medulla by secretion into the pars recta or descending limb of long-looped nephrons and reabsorption from the ascending limb and/or medullary collecting duct. Evidence supporting the recycling hypothesis is summarized and the process is analyzed quantitatively by an examination of the mass flow of potassium reaching different sites along superficial and juxtamedullary nephrons and collecting tubules. From differences in potassium mass flow between sites, we have estimated the amount of potassium that must be secreted or absorbed by individual segments of the renal tubule. These rates of secretion and absorption are compared with the potassium transport characteristics of the respective segments, as assessed by isolated tubule perfusion in vitro and micropuncture in vivo. It is apparent that potassium secretion can occur passively in the pars recta and descending limb of long-looped nephrons as a consequence of the elevated potassium concentration in the medullary interstitium. At present, no active potassium absorptive mechanism has been demonstrated in any segment of the ascending limb. Due to the very high ionic permeability of the thin ascending segment and the lumen-positive transepithelial voltage in the thick ascending segment, however, considerable passive absorption likely occurs, although net potassium secretion has also been demonstrated in the cortical thick ascending limb. The high potassium concentration in the inner medullary interstitium and the difference in mass flow of potassium between the end of superficial nephrons in the cortex and the collecting ducts in the papilla, at least under certain circumstances, are best accounted for by net potassium reabsorption in the medullary collecting duct.
Anion permeabilities of the isolated perfused rabbit proximal tubule
Authors: Warnock D. G. , Yee V. J.
Published: December 2017

Electrophysiologic and isotopic techniques were used to characterize the anion permeabilities of isolated perfused rabbit proximal tubules (S2 segments). Tubules were differentiated into chloride- and sodium-selective populations by electrophysiologic rather than by anatomic criteria. The tubules were studied under conditions that inhibited active sodium transport. The isotopic chloride permeability coefficient was 5.5 +/- 0.6 X 10(-5) cm/s (n = 19) for chloride-selective tubules and 3.2 +/- 0.6 X 10(-5) cm/s (n = 15) for sodium-selective tubules. The isethionate permeability coefficient was 1.1 +/- 0.2 X 10(-5) cm/s (n = 23) and did not vary with sodium or chloride selectivity. The variation of oxyanion permeability (bicarbonate, isethionate, and cyclamate) relative to chloride resulted from changes in chloride permeability, per se, rather than any change in the oxyanion permeability. A consistent relation between bicarbonate and isethionate permeability permitted the permeability of bicarbonate ion to be estimated at 1.3 X 10(-5) cm/s. The mechanism of ion selectivity appears to be different for the two populations of tubules. Chloride-selective tubules appear to hve relatively small pathways that do not contain fixed-charge sites. In contrast, sodium-selective tubules may have permeation pathways that contain fixed negative-charge sites.
Effects of acute potassium infusions with salts other than chloride on plasma renin activity
Authors: Kirchner K. A. , Mueller R.
Published: December 2017

To evaluate the contribution of chloride to the suppression of plasma renin activity (PRA) by KCl, PRA was measured before and after venous infusions of KCl, KHCO3, KNO3, and KC2H3O2 in dietary NaCl-restricted rats. In contrast to controls, PRA decreased (P less than 0.02) after infusion of each potassium salt [KCl from 55.3 +/- 6.4 to 27.0 +/- 6.4 ng.ml-1.h-1 (mean +/- SE); KC2H3O2 from 39.3 +/- 4.0 to 20.6 +/- 4.0; KHCO3 from 64.4 +/- 6.2 to 47.2 +/- 6.2; KNO3 from 40.0 +/- 4.0 to 18.6 +/- 4.0]. Arterial pressure, plasma volume, inulin clearance, serum sodium concentration, and net sodium balance were not different between control and potassium-infused groups. Potassium loading did not increase absolute or fractional sodium excretion. PRA failed to decrease in animals given an equal volume of NaNO3. Furosemide prevented the fall in PRA associated with potassium loading despite replacement of urinary losses. These results suggest that the decrease in PRA observed during potassium loading occurs through the macula densa mechanism but is not dependent on concomitant chloride administration. As furosemide prevents the fall in PRA, macula densa chloride transport may be necessary for potassium to exert this effect.
Na and K transport across the cortical and outer medullary collecting tubule of the rabbit: evidence for diffusion across the outer medullary portion
Authors: Stokes J. B.
Published: December 2017

The rabbit collecting tubule displays functional axial heterogeneity with respect to Na ion transport. The present experiments compared cortical collecting tubule (CCT) and outer medullary collecting tubule (OMCT) Na and K transport. Na efflux across the CCT was inhibited by ouabain, whereas Na efflux across the OMCT was smaller and unaffected by ouabain. Assessment of the equivalent conductivities of Na and K across the CCT by imposition of a Na-K bi-ionic gradient demonstrated a higher K/Na conductivity across the CCT than would be predicted from their respective limiting equivalent conductivities in water. In contrast, the ratio of their conductivities across OMCT were not different than would be predicted by their ratio in water. The "selective" nature of the Na and K pathways across CCT was confirmed by measuring the tracer efflux rate coefficients. In the amiloride-treated CCT the K/Na rate coefficient ratio was 9.8 +/- 1.5; this ratio across the OMCT was 1.51 +/- 0.10. The latter value is not different from the ratio of the mobilities of these ions in water. The diffusional nature of Na and K transfer across OMCT was confirmed by the demonstration of the concentration-independent Na efflux rate coefficient and the demonstration of appropriate net Na and K transepithelial flows in response to imposition of oppositely directed chemical gradients. Although the permeability of the OMCT is low, the chemical gradients found in vivo might be sufficient to effect some K absorption and Na secretion without completely dissipating the steep gradients generated by the CCT. These transport characteristics might be important in the regulation of Na excretion and K recycling into the renal medulla.
In vivo proximal tubular fluid-to-plasma chloride concentration gradient in the rabbit
Authors: Vari R. C. , Ott C. E.
Published: December 2017

It has been reported that the concentration of chloride in the proximal tubule is greater than that in plasma in several mammalian species. Much of the theory concerning fluid and electrolyte reabsorption in the proximal tubule is based on data taken from in vitro isolated proximal tubules of the rabbit nephron. This study measured in vivo the rabbit proximal tubule fluid-to-ultrafiltrate chloride concentration ratio [(TF/UF)Cl] and its relationship to proximal tubule length as estimated by the tubule fluid-to-plasma inulin concentration ratio [(TF/P)In]. From six rabbits, 19 random proximal tubules were micropunctured and analyzed for inulin and chloride concentrations, the latter being measured by microelectrometric titration. Plasma ultrafiltrate was determined by correcting plasma chloride concentration for protein concentration. The average single nephron filtration rate was 20.2 +/- 0.8 nl/min. The (TF/UF)Cl ratio was 1.10 +/- 0.03, which was significantly different from unity. Furthermore, regression analysis yielded no significant correlation between the (TF/UF(Cl and (TF/P)In ratio. This study demonstrates that a tubule lumen-to-plasma chloride concentration gradient exists in the in vivo proximal tubule of the rabbit that is apparently established early and is not correlated with proximal tubule length.
Temperature-induced conversion of the renal adrenoreceptor: modulating renin release
Authors: Corwin E. J. , Cho K. W. , Malvin R. L.
Published: December 2017

The release of renin from dog cortical kidney slice preparations incubated in a physiological salt solution can be modulated by alpha- and beta-adrenergic drugs. When given to slices maintained at 37 degrees C, the beta-agonists isoproterenol (ISP) and norepinephrine stimulated renin release from the slices. When the slices were maintained at 20 degrees C, the beta-agonists had no effect on renin release. However, the alpha-agonist phenylephrine inhibited renin release from the slices incubated at 20 degrees C in a dose-dependent manner, whereas its effect on slices incubated at 37 degrees C was less pronounced. The change in response of the slices from beta dominant at 37 degrees C to alpha dominant at 20 degrees C appeared to be a receptor phenomenon. When the cortical slices were incubated with the irreversible alpha-antagonist phenoxybenzamine (POB) at 20 degrees C for 1 h, they were unable to respond to ISP when returned to 37 degrees C. However, POB had no effect on the response of slices to ISP when given at 37 degrees C. It appears that with a decrease in temperature the renal beta-receptors demonstrate properties normally associated with alpha-receptors, namely the potential to be blocked by POB. This may be due to an interconversion of the renal alpha- and beta-adrenoceptors.
Skeletal muscle injury after magnesium depletion in the dog
Authors: Cronin R. E. , Ferguson E. R. , Shannon W. A. , Knochel J. P.
Published: December 2017

Magnesium deficiency was induced in a setting of an otherwise adequate diet in adult beagle dogs. Despite the development of severe hypomagnesemia (from 1.5 +/- 0.2 to 0.5 +/- 0.2 meq/liter) during the 10-wk study, Mg content of skeletal muscle fell only modestly (from 3.8 +/- 0.2 to 3.1 +/- 0.4, P less than 0.005, at 7 wk and 3.5 +/- 0.4 mM/100 g FFDS, NS, at 10 wk). The most pronounced muscle compositional changes were a loss of phosphorus (from 29.5 +/- 1.8 to 22.0 +/- 1.6, P less than 0.001, at 7 wk and 24.8 +/- 2.8 mM/100 G FFDS, P less than 0.001, at 10 wk) and gains of calcium (from 0.64 +/- 0.11 to 0.93 +/- 0.17, P less than 0.05, at 7 wk, and 0.85 +/- 0.26 mM/100 g FFDS, P less than 0.05, at 10 wk), sodium (from 13.2 +/- 2.6 to 22.9 +/- 4.7, P less than 0.001 at 7 wk and 17.8 +/- 2.0 meq/100 g FFDS, P less than 0.005, at 10 wk), and chloride (from 5.8 +/- 0.8 to 8.2 +/- 1.6, P less than 0.001, at 7 wk and 6.8 +/- 0.6 meq/100 g FFDS, P less than 0.05, at 10 wk). Cellular potassium content did not change (from 35.9 +/- 1.9 to 33.0 +/- 4.1, NS, at 7 wk and 36.3 +/- 2.0 meq/100 g FFDS, NS, at 10 wk). Muscle cell electrical hyperpolarization developed after 10 wk of Mg depletion. Convulsive seizures developed in three animals. Frank rhabdomyolysis in three animals and focal necrosis in four animals were present on terminal biopsy, with only four animals having completely normal histology.
Effects of arginine vasopressin on the thin ascending limb of Henle's loop of hamsters
Authors: Imai M. , Kusano E.
Published: December 2017

Arginine vasopressin (AVP) has been shown to stimulate active Cl transport across the medullary thick ascending limb of Henle's loop (MAL) in association with an increase in adenylate cyclase activity. To determine whether the failure to demonstrate active Cl transport across the thin ascending limb of Henle's loop (TAL) in previous in vitro perfusion studies was due to the absence of AVP in the preparation, we examined the effect of AVP on adenylate cyclase activity and Cl transport in the hamsters TAL. AVP (1 mU/ml) increased adenylate cyclase activity in the hamster TAL (20.7 +/- 5.2 control vs. 46.2 +/- 10.1 fmol . mm-1 . 30 min-1, n = 6, P less than 0.05) but not in the descending limb (27.8 +/- 7.0 control vs. 20.4 +/- 2.7, n = 4, P less than 0.05). When both MAL and TAL were perfused, a lumen-positive transepithelial voltage (Vt) was observed. The Vt was increased by adding 1 or 10 mU/ml AVP to the bath. When only the TAL was perfused, the Vt was not different from zero. Similar results were obtained in mouse renal tubules. In other experiments, AVP did not affect the diffusion potential generated when a transepithelial NaCl gradient was present. AVP or dibutyryl cAMP caused little or no change in efflux of radioactive chloride across the hamster TAL. These findings suggest that electrogenic chloride transport is not demonstrable in the TAL even in the presence of AVP. The physiologic role of AVP-sensitive adenylate cyclase in the TAL remains to be established.
Influence of thiopental anesthesia on renal sodium and water excretion in the dog
Authors: Gagnon J. A. , Felipe I. , Nelson L. D. , Butkus D. E.
Published: December 2017

The influence of thiopental anesthesia on renal tubular sodium reabsorption was investigated in the well-trained dog. After administration of the anesthetic, renal sodium reabsorption was depressed, leading to the enhanced excretion of sodium and water. Associated with this response was a decrease in the plasma levels of epinephrine and norepinephrine. Neither renal hemodynamic functions nor the humoral factors, prostaglandin E, plasma renin activity, or arginine vasopressin appeared to be the major determinants of the natriuresis. These observations suggest that the administration of thiopental depresses renal sympathetic nerve activity, thereby diminishing the renal tubular transport of sodium.
Distribution of enzymes of adenylate and guanylate nucleotide metabolism in rat nephron
Authors: Cole B. R. , Hays A. E. , Boylan J. G. , Burch H. B. , Lowry O. H.
Published: December 2017

In a previous study of discrete segments of rat nephron, we reported the levels of high-energy adenylate and guanylate phosphates to be highest in the distal straight and convoluted tubules. Those findings stimulated the study of the distribution of seven enzymes involved in the following metabolic pathways of these nucleotides [Formula: see text]. The patterns of distribution of enzymes in each pathway differed greatly. The phosphodiesterases, 1 and 2, were high in glomeruli and distal tubular segments and low in proximal segments. Adenylate kinase, 3, in contrast, was high in glomeruli, proximal segments, thick ascending limb of Henle, and distal convoluted tubules. Guanylate kinase levels, 4, however, were similar in all segments. The pattern of nucleosidediphosphate kinase, 5, was high in proximal convoluted, thick ascending limb, and distal convoluted tubules. The pattern of the degradative enzyme, 5'-nucleotidase, 6, whose levels were highest in proximal segments, was opposite from that of AMP deaminase, 7, highest in the distal nephrons. These dissimilar patterns underscore the extent of nephron heterogeneity.
Redox state of cytochrome aa3 in isolated perfused rat kidney
Authors: Epstein F. H. , Balaban R. S. , Ross B. D.
Published: December 2017

Optical spectroscopy was used to evaluate mitochondrial anoxia in the isolated perfused rat kidney by determining the percentage of cytochrome aa3 in the reduced state. Despite high levels of plasma flow (greater than 20 ml . g-1 . min-1) and venous PO2 (greater than 300 mmHg), 25--40% of cytochrome aa3 appeared to be in its reduced form. Agents that alter metabolism or transport primarily in renal cortex had little or no effect on the redox state of cytochrome aa3. These included 3-mercaptopicolinate, an inhibitor of gluconeogenesis; 2-tetradecylglycidic acid, an inhibitor of fat metabolism via carnitine-fatty acyltransferase, and acetazolamide. In contrast, a decrease in medullary transport induced by the loop diuretics bumetanide or furosemide produced an increase in cytochrome aa3 oxidation consistent with a decrease in transport-related oxygen consumption in the hypoxic area. The results suggest that substantial portions of the kidney, particularly in the renal medulla, may normally operate on the brink of anoxia despite high PO2 in artery and vein.
Effect of respiratory alkalosis on renal phosphate excretion
Authors: Hoppe A. , Metler M. , Berndt T. J. , Knox F. G. , Angielski S.
Published: December 2017

Respiratory alkalosis induced hypophosphatemia and hypophosphaturia in intact animals. The present studies evaluated the effect of respiratory alkalosis on tissue phosphate distribution and renal phosphate transport in the presence and absence of parathyroid hormone (PTH). Respiratory alkalosis decreased plasma phosphate concentration and increased phosphate concentrations in muscle and liver. It decreased fractional phosphate excretion (FEPi) from 6.1 +/- 1.4 to 0.6 +/- 0.2%. In thyroparathyroidectomized (TPTX) rats infused with 20 mM phosphate, respiratory alkalosis decreased FEPi from 15.0 +/- 0.9 to 5.5 +/- 0.1%. PTH or dibutyryl cAMP administration produced a phosphaturia that was blunted by respiratory alkalosis. The phosphaturic response to PTH was also blunted in hypocapnic rats in which alkalosis was prevented by infusion of HCl. We conclude that respiratory alkalosis increases phosphate uptake by muscle, which largely accounts for the hypophosphatemia. The kidney response with increased phosphate reabsorption independent of plasma and kidney phosphate concentrations and with refractoriness to the phosphaturic effect of PTH. This refractoriness to the phosphaturic effect of PTH is due to decreased PCO2 rather than to the concomitant extracellular alkalosis.