bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the pituitary in reflex natriuresis following acute unilateral nephrectomy
Authors: Lin S. Y. , Wiedemann E. , Humphreys M. H.
Published: December 2017

We studied the role of altered pituitary function in the reflex natriuresis that occurs after acute unilateral nephrectomy (AUN). In normal rats, AUN increased both sodium (UNaV) and potassium excretion within 90 min. In hypophysectomized rats, no increase in cation excretion after AUN occurred, results which were duplicated in rats in which pituitary function was altered by prior treatment with dexamethasone (2 mg/kg ip for 3 days). In adrenalectomized rats, AUN led to increases in cation excretion similar to those seen in normal rats, indicating that intact adrenal function was not necessary for this excretory response following AUN. These changes in cation excretion were correlated with measurements in peripheral plasma of two peptides derived from the pituitary precursor molecule pro-opiomelanocortin (POMC). Radioimmunoassayable plasma beta-endorphin failed to change after AUN in any of the conditions studied. However, a sensitive radioimmunoassay for the N-terminal fragment (NTF) of POMC indicated that plasma NTF rose significantly after AUN in normal and adrenalectomized rats but did not change in hypophysectomized, steroid-pretreated, or shamoperated rats. The increase in NTF concentration correlated with the increase in UNaV after AUN. These results demonstrate that the reflex increase in cation excretion after AUN is dependent on an intact pituitary gland and is associated with an increase in peripheral plasma concentration of NTF. NTF, or some other peptide residing in the N-terminal portion of POMC, could promote the natriuresis after AUN; the importance of the pituitary gland in this response could be the secretion of this peptide.
Synthetic atrial natriuretic factor decreases renal tubular phosphate reabsorption in rats
Authors: Hammond T. G. , Haramati A. , Knox F. G.
Published: December 2017

Atrial natriuretic factor (ANF), a family of peptides isolated from cardiac atria, has marked effects on sodium excretion. A synthetic 26 amino acid sequence of ANF peptide has also been shown to be phosphaturic. However, it is difficult to assess whether the phosphaturia is due to changes in tubular reabsorption of phosphate without control of filtered load of phosphate. In the present study, the hypothesis that ANF peptide decreases tubular phosphate reabsorption was tested by using graded phosphate infusions of 0, 1, 2, and 3 mumol/min in thyroparathyroidectomized rats. Further, reabsorbed phosphate was similarly assessed in rats infused with parathyroid hormone (PTH) to allow comparison with a known phosphaturic hormone. ANF peptide decreased reabsorbed phosphate compared with saline controls (2.72 +/- 0.28 mumol/ml GFR compared with 3.35 +/- 0.35, P less than 0.05) but not as much as a maximally phosphaturic dose of PTH (2.04 +/- 0.13 mumol/ml GFR). We conclude that synthetic ANF peptide decreases tubular phosphate reabsorption in vivo.
Na+ gradient-dependent glycine uptake in basolateral membrane vesicles from the dog kidney
Authors: Schwab S. J. , Hammerman M. R.
Published: December 2017

The imposition of a Na+ gradient (extravesicular greater than intravesicular) stimulated the uptake of [3H]glycine measured over time in basolateral membrane vesicles from dog kidney over that measured in the presence of a choline+ gradient or measured under Na+-equilibrated conditions. Na+ gradient-dependent uptake of [3H]glycine was stimulated by an intravesicular-negative membrane potential. Efflux of [3H]glycine was enhanced by an intravesicular-positive membrane potential. Substrate velocity analysis of net Na+-dependent [3H]glycine uptake over the range of amino acid concentrations from 10 to 500 microM demonstrated a single saturable transport system with apparent Km = 84 microM and apparent Vmax = 143 pmol [3H]glycine X mg protein-1 X 15 s-1. Counterflow of [3H]glycine was demonstrated in the presence of Na+ when basolateral vesicles were preloaded with glycine but not with L-alanine or L-proline. These findings are consistent with carrier-mediated, electrogenic cotransport of Na+ and glycine in basolateral vesicles. Unlike the case for [3H]glycine, Na+ gradient-dependent uptake of neither L-[3H]alanine nor L-[3H]proline was observed in basolateral vesicles. Na+ gradient-dependent uptake of all three amino acids was demonstrated in brush border vesicles from the dog kidney. We conclude that variability exists between basolateral and brush border membranes in terms of the presence or absence of Na+-dependent transport systems for specific amino acids. This variability probably reflects differences between the functional significances of the Na+-dependent transport processes in the two membranes.
NAD-glycohydrolase in renal brush border membranes
Authors: Kempson S. A.
Published: December 2017

NAD is hydrolyzed during incubation with isolated renal brush border membranes (BBM). The specific enzymatic mechanisms have not been identified apart from the activity of ADP-ribosyltransferase, which accounts for a very small proportion of the total hydrolysis. In the present study, an NAD-glycohydrolase (NGH) was identified in the renal BBM using the cyanide-addition assay to monitor hydrolysis of NAD at the nicotinamide-ribose bond. The production of nicotinamide and ADP-ribose, the expected reaction products, was determined by thin-layer chromatography. The NGH was enriched ninefold in the BBM fraction and accounted for 36% of the total rate of NAD hydrolysis by BBM enzymes at pH 7.4. Assay of NGH in sealed BBM vesicles subjected to osmotic shock indicated that about 23% of the NGH is exposed on the cytoplasmic surface of the BBM. The enzyme was inhibited by nicotinamide in vitro and also when the nicotinamide was administered in vivo, suggesting, indirectly, that the enzyme may play a role in mediating the effects of nicotinamide on BBM phosphate transport.
Intracellular pH in the isolated perfused rabbit proximal straight tubule
Authors: Sasaki S. , Shigai T. , Takeuchi J.
Published: December 2017

For the purpose of measuring the intracellular pH (pHi) of the mammalian renal proximal tubule, a liquid membrane pH microelectrode was made using a neutral hydrogen ion-selective carrier. The pHi of the rabbit proximal straight tubule perfused in vitro with a solution containing 25 mM HCO3- was 7.22 +/- 0.03. We noted a value significantly lower than the bath pH of 7.44 +/- 0.02 but significantly higher than the pHi of 6.62 +/- 0.03 predicted for passive H+ distribution. Replacement of luminal Na+ with choline quickly (within 1 min) decreased pHi from 7.25 +/- 0.05 to 7.10 +/- 0.05 (P less than 0.001). This change was reversible when Na+ was added again in the luminal solution. A reduction of luminal Na+ from 20 mM to 0 also reduced pHi from 7.15 +/- 0.06 to 7.04 +/- 0.08, and this pHi reduction was blocked by luminal addition of 1 mM amiloride. However, pHi reduction induced by luminal Na+ removal was not affected by luminal addition of 1 mM SITS. Replacement of bath Na+ with choline also reversibly reduced pHi from 7.27 +/- 0.02 to 7.15 +/- 0.02 (P less than 0.001), but this change was totally blocked by the presence of 1 mM SITS. Accordingly, these data suggest that a Na+-H+ exchanger exists in the luminal membrane of the intact rabbit proximal straight tubule.
Kinin effects on electrogenic ion transport in primary cultures of pig renal papillary collecting tubule cells
Authors: Cuthbert A. W. , George A. M. , MacVinish L.
Published: December 2017

Confluent monolayers of pig renal papillary collecting tubule (RPCT) cells were formed on Millipore filters coated with collagen. They were clamped in Ussing-type chambers and used to measure short-circuit current (SCC). The monolayers had low potentials (0.1 mV) with the basolateral side positive. Small inward currents flowed under short-circuit conditions. Increases in SCC were obtained following addition of a number of agents. Receptors associated with SCC changes were disposed as follows: for kinins (e.g., lysyl-bradykinin) they were present on both sides of the tissue, while those for arginine vasopressin and norepinephrine were present on the basolateral side only. Epithelia responded to PGE2 added to the apical or basolateral face of the tissue; application to one side prevented the response from the contralateral side. The tissues also responded to forskolin, an activator of adenylate cyclase, with a sustained inward current that was sensitive to furosemide. Similar sustained inward currents were recorded following exposure to 8-bromoadenosine-3',5'-cyclic monophosphate (BrcAMP). Responses to kinins were attenuated by inhibition of fatty acid cyclooxygenase with either indomethacin or piroxicam or by replacing chloride with impermeant ions. If the SCC was first increased with forskolin, BrcAMP, or norepinephrine, the kinin effects on SCC were either abolished or reversed. It is concluded that kinin can cause chloride secretion in RPCT monolayers, possibly via a prostaglandin or a prostaglandin-adenylate cyclase mechanism. Secondary effects of kinin, exposed by first raising tissue cAMP levels, are not precluded.
Forskolin and antidiuretic hormone stimulate a Ca2+-activated K+ channel in cultured kidney cells
Authors: Guggino S. E. , Suarez-Isla B. A. , Guggino W. B. , Sacktor B.
Published: December 2017

Single channels in the apical cell membrane of primary cultured chick kidney cells were studied using the patch clamp technique. Cell-attached recordings revealed the presence of a 107 +/- 6 pS channel that increased fractional open time upon depolarization. Experiments with inside-out excised patches indicated that the channel is K+ selective, Ca2+ activated, and inhibited by Ba2+. The addition of forskolin or antidiuretic hormone (ADH) to the bath during cell-attached recordings caused an increase in the fractional open time of the channel. The activation of a K+ channel by increases in cAMP may be one way in which K+ secretion in the kidney is stimulated by ADH in vivo.
Effects of acute uninephrectomy and age on renal blood flow autoregulation in the rat
Authors: Chevalier R. L. , Kaiser D. L.
Published: December 2017

We previously showed that renal autoregulatory behavior is modified by both normal and compensatory renal growth. To determine whether the hemodynamic changes precede an increase in renal mass, the relationship of renal blood flow (RBF) to renal perfusion pressure (RPP) was examined in the remaining kidney of anesthetized young and adult rats 30 min following contralateral nephrectomy. In young control animals 32-41 days old, an autoregulation factor (AF) of 0.37 +/- 0.10 (SE) over RPP 70-100 mmHg indicates efficient autoregulation and did not change during the experiment. Acute uninephrectomy in young hydropenic rats resulted in a 16% increase in RBF at normal RPP, and AF increased to 1.22 +/- 0.34 for RPP 70-100 mmHg, reflecting marked impairment of autoregulation. In young animals in which saline infusion was not reduced at the time of uninephrectomy, RBF increased 22% at normal RPP, and autoregulation was similarly impaired (AF 0.92 +/- 0.12 for RPP 70-100 mmHg). Acute uninephrectomy in adult rats resulted in a 13% increase in RBF, with better preservation of AF (0.48 +/- 0.09) over the adult autoregulatory range (RPP 100-130 mmHg). These findings indicate that profound hemodynamic changes take place in the remaining kidney within 30 min of acute uninephrectomy and that they are qualitatively similar to those observed after compensatory hypertrophy has developed.
Ontogeny of Na-K-ATPase activity in thick ascending limb and of concentrating capacity
Authors: Rane S. , Aperia A.
Published: December 2017

Na-K-ATPase activity in the thick ascending limb of Henle (TAL) and the capacity to concentrate urine was determined in 12-, 16-, 20-, 30-, and 40-day-old rats. The most pronounced increase in enzyme activity occurred between 16 and 20 days of age. The relation between enzyme activity in the cortical and medullary TAL was found to be the same in 16-, 20-, and 40-day-old rats, and most enzyme determinations were made in the medullary TAL. The development of Na-K-ATPase activity in TAL and urinary concentrating capacity followed the same pattern. The developmental increase in Na-K-ATPase activity and concentrating capacity between 16 and 20 days of age was accompanied by an increase in serum corticosterone level and was abolished by adrenalectomy. Treatment with glucocorticoid hormones precociously induced Na-K-ATPase activity and concentrating capacity in 13- to 16-day-old rats but had no effect on Na-K-ATPase activity in 17- to 20-day-old rats. The increase in enzyme activity from 20 to 40 days of age was accompanied by an increase in the single nephron glomerular filtration rate. The results suggest that Na-K-ATPase activity in the TAL is an important determinant of the concentrating capacity during development. The developmental surge in Na-K-ATPase activity and concentrating capacity between 16 and 20 days of age is probably set off by the rise in the serum corticosterone level.
Vascular and renal effects of leukotriene C4 in conscious rats
Authors: Filep J. , Rigter B. , Frolich J. C.
Published: December 2017

To investigate the possible renal effects of leukotriene C4 (LTC4) renal function was monitored in conscious unrestrained rats. Intravenous injections of 2, 4, and 8 micrograms/kg LTC4 markedly and dose-dependently elevated urine flow (by 64, 91, and 133%, respectively) with a concomitant increase in urinary sodium (61, 81, and 118%) and potassium (39, 50, and 76%) excretion. All changes were statistically significant. There was a tendency for glomerular filtration rate to increase, but this change reached statistical significance only after the highest dose of LTC4. Moreover, 8 micrograms/kg LTC4 reduced p-aminohippurate clearance by 33%. A dose-dependent increase in mean arterial pressure (15 mmHg at 2 micrograms/kg, 20 mmHg at 4 micrograms/kg, and 30 mmHg at 8 micrograms/kg) was observed following LTC4 administration. While the administration of FPL 55712, a putative antagonist of leukotrienes, had no effect on mean arterial pressure and kidney function, it significantly attenuated the vasopressor effect of LTC4 and practically completely abolished LTC4-induced changes in both renal hemodynamics and water and electrolyte excretion. These results raise the possibility that leukotrienes might be involved in the regulation of renal hemodynamics and could modify urinary electrolyte excretion under conditions in which leukotriene formation is enhanced.
Urate transport in the proximal tubule: in vivo and vesicle studies
Authors: Kahn A. M. , Weinman E. J.
Published: December 2017

The transport of urate in the mammalian nephron is largely confined to the proximal tubule. Depending on the species, net reabsorption or net secretion is observed. The rat, like the human and the mongrel dog, demonstrates net reabsorption of urate and has been the most extensively studied species. The unidirectional reabsorption and secretion of urate in the rat proximal tubule occur via a passive and presumably paracellular route and by a mediated transcellular route. The reabsorption of urate, and possibly its secretion, can occur against an electrochemical gradient. A variety of drugs and other compounds affect the reabsorption and secretion of urate. The effects of these agents depend on their site of application (luminal or blood), concentration, and occasionally their participation in transport processes that do not have affinity for urate. Recent studies with renal brush border and basolateral membrane vesicles from the rat and brush border vesicles from the dog have determined the mechanisms for urate transport across the luminal and antiluminal membranes of the proximal tubule cell. Brush border membrane vesicles contain an anion exchanger with affinity for urate, hydroxyl ion, bicarbonate, chloride, lactate, p-aminohippurate (PAH), and a variety of other organic anions. Basolateral membrane vesicles contain an anion exchanger with affinity for urate and chloride but not for PAH. Both membrane vesicle preparations also permit urate translocation by simple diffusion. A model for the transcellular reabsorption and secretion of urate in the rat proximal tubule is proposed. This model is based on the vesicle studies, and it can potentially explain the majority of urate transport data obtained with in vivo techniques.
Contributions of glomerular and tubular mechanisms to antidiuresis in conscious domestic fowl
Authors: Stallone J. N. , Braun E. J.
Published: December 2017

Recently developed radioimmunoassay (RIA) techniques were employed in a quantitative investigation of the renal actions of the avian antidiuretic hormone arginine vasotocin (AVT) in the conscious domestic fowl. Constant intravenous infusion of AVT at doses of 0.125-1.00 ng X kg-1 X min-1 was used to produce plasma AVT (PAVT) concentrations (verified by RIA) over the entire range of physiological PAVT levels in the domestic fowl. Comparison of the dose-response relationships between PAVT and glomerular and tubular mechanisms of antidiuresis revealed that tubular mechanisms are of primary importance and glomerular mechanisms of secondary importance in the conservation of water by the avian kidney. The greatest proportion of the total AVT-induced reduction in renal water excretion occurred at low physiological PAVT levels (less than 5 microU/ml), prior to any significant reduction in glomerular filtration rate (GFR), and appeared to be the exclusive result of tubular mechanisms of antidiuresis. At high PAVT levels (5-16 microU/ml), glomerular and tubular mechanisms overlapped, and their effects on water conservation could not be separated. Although GFR was reduced by nearly 30% at the highest dose of AVT, only minor additional amounts of water were conserved by the combined actions of glomerular and tubular mechanisms. Thus glomerular mechanisms appear to have only a minor secondary effect on water-conserving ability of the avian kidney.
Transport of N1-methylnicotinamide across brush border membrane vesicles from rabbit kidney
Authors: Wright S. H.
Published: December 2017

A preparation of isolated brush border membranes from the rabbit renal cortex was used to examine the characteristics of N1-methylnicotinamide (NMN) transport in the kidney. Transport was independent of the presence of Na+ under Na+ equilibrium conditions. However, outwardly directed Na+ gradients stimulated NMN uptake, whereas inwardly directed Na+ gradients inhibited NMN uptake. Transport appeared to involve two parallel processes: one saturable with a Jmax of 5 nmol X mg protein-1 X min-1 and an apparent Kt of 0.6 mM, and a second that behaved like passive diffusion. Countertransport of NMN was observed when vesicles were preloaded with either NMN or another organic cation, tetraethylammonium (TEA). TEA and several structural analogues, as well as a wide variety of other organic cations and bases, were effective inhibitors of NMN uptake, though nicotinamide and p-aminohippuric acid did not interact with the uptake process. Outwardly directed proton gradients (pH 6.0 in, 7.6 out) stimulated transport, suggesting that NMN uptake may involve a countertransport of H+. The electrical potential difference across the vesicle membrane was manipulated using gradients of the permeant organic ion thiocyanate (SCN-); an outwardly directed gradient of SCN- (i.e., a depolarizing condition) stimulated uptake and produced a transient accumulation of NMN above that noted at equilibrium, whereas an inwardly directed SCN- gradient inhibited uptake of NMN. The data can be explained by postulating the presence of an electrogenic NMN+-H+ antiporter in the rabbit luminal membrane that could play a role in organic cation secretion.
Extrarenal handling of phosphate: effect of thyroparathyroidectomy, 1,25-dihydroxycholecalciferol, and dietary calcium
Authors: Troehler U. , Bonjour J. P. , Fleisch H.
Published: December 2017

It is known that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] mobilizes inorganic phosphate (Pi) from gut and bone, thus increasing the entry of Pi into the extracellular space (ECS). In this work, we have investigated whether 1,25(OH)2D3 could also facilitate the net exit of Pi out of this pool into certain soft tissue and/or bone compartments in thyroparathyroidectomized (TPTX) rats. Sham-operated, TPTX, and TPTX rats treated with 1,25(OH)2D3 (26 pmol/day ip for 1 wk) were infused with a known amount of Pi over a given time. The amount of Pi excreted in the urine in excess of base-line values and the rise of the phosphatemia ([Pi]p) were measured. The difference between these two parameters corresponded to the net retention of infused Pi in the whole animal (RAPi) for a given rise in [Pi]p. The results show that RAPi was markedly diminished in TPTX as compared with sham-operated animals. This decrease could be corrected by 1,25(OH)2D3 treatment. Chronic reduction in the level of calcemia in TPTX 1,25(OH)2D3-supplemented rats as induced by decreasing dietary Ca intake also diminished RAPi. These effects could not be ascribed to the known actions of the experimental maneuvers on the renal excretion of Pi. Since infusions were chosen to obtain similar rises in [Pi]p and started from same levels of [Pi]p in animals of the same weight, the differences in RAPi were not due to variation of Pi retention in the ECS.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal sodium handling in normal humans subjected to low, normal, and extremely high sodium supplies
Authors: Roos J. C. , Koomans H. A. , Dorhout Mees E. J. , Delawi I. M.
Published: December 2017

We studied renal sodium handling, extracellular fluid volume (ECFV), plasma renin activity, aldosterone and norepinephrine, and blood pressure in eight healthy volunteers after equilibration on intakes of 20, 200, and 1,128 +/- 141 meq sodium, respectively. Renal sodium handling was assessed by means of clearance studies during maximal water diuresis and lithium clearance. Urinary sodium excretions were 22 +/- 4, 202 +/- 19, and 1,052 +/- 86 meq/day. From the lower to the upper sodium intake level, 24-h creatinine clearance rose from 111 +/- 7 to 136 +/- 11 ml/min and inulin clearance from 103 +/- 9 to 129 +/- 9 ml/min, whereas proximal and distal fractional sodium reabsorption (FSRprox and FSRdist, respectively) fell from 86.8 +/- 1.3 to 79.0 +/- 2.7% and from 96.5 +/- 0.5 to 76.0 +/- 1.9%, respectively. During the normal sodium intake (200 meq), intermediate values were recorded. The changes in fractional lithium clearance were less consistent but correlated with FSRprox (r = 0.78, P less than 0.001) and not with FSRdist. Major changes in plasma renin activity, aldosterone, and, to a lesser extent, norepinephrine accompanied these changes in kidney function, displaying inverse and exponential correlations with daily sodium excretion and ECFV. No consistent rise in blood pressure was detected. These observations indicate that in healthy humans renal adaptation to vast variations in sodium intake includes resetting of glomerular filtration rate, FSRprox, and, in particular, FSRdist. Alterations in neurohumoral factors may play a dominant role in this adaptation.
Alpha 2-adrenoceptor stimulation and cellular cAMP levels in microdissected rat glomeruli
Authors: Umemura S. , Smyth D. D. , Pettinger W. A.
Published: December 2017

A functional role for the numerically predominant glomerular alpha 2-adrenoceptors is unknown. In other tissues, activation of alpha 2-adrenoceptors inhibits adenylate cyclase activity. We therefore examined the effect of alpha 2-adrenoceptor stimulation with (-)-epinephrine (E) on the cellular cAMP concentration in glomeruli isolated by microdissection. Parathyroid hormone (1-34 PTH), prostaglandin E2 (PGE2), histamine, serotonin, or adenosine, in the presence of 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor) and propranolol, was used to activate adenylate cyclase in single intact rat glomeruli. alpha 2-Adrenoceptors were activated with varying concentrations of E (37 degrees C, 2 min). In the presence of PTH-stimulated cAMP production, alpha 2-adrenoceptor activation with E (5 X 10(-7) to 5 X 10(-6) M) suppressed cellular cAMP levels in a dose-dependent fashion with the maximum at 30%. This suppression by E was inhibited by 5 X 10(-6) M yohimbine but not by 5 X 10(-6) M prazosin, confirming alpha 2-adrenoceptor mediation of this effect of E. Consistent with the above findings, the specific alpha 2-adrenoceptor agonist BHT933 inhibited PTH-stimulated cAMP accumulation. E also inhibited cAMP accumulation stimulated by serotonin. However, E did not suppress the PGE2-, histamine-, or adenosine-stimulated increase in cellular cAMP in the glomerulus. Activation of alpha 2-adrenoceptors inhibits cAMP formation stimulated by PTH or serotonin but not by PGE2, histamine, or adenosine in the rat glomerulus. Thus, the ability of alpha 2-adrenoceptors to inhibit adenylate cyclase appears to be hormone and probably function specific.
Can causality be determined from proximal tubular reabsorption and peritubular physical factors?
Authors: Tucker B. J. , Mundy C. A. , Blantz R. C.
Published: December 2017

Many studies in the literature have drawn conclusions regarding the mechanism of change in absolute proximal tubular reabsorption (APR) based on steady-state measurements of proximal reabsorptive rates and the peritubular capillary. The proximal reabsorptive rate, APR, is the product of the effective reabsorptive pressure (ERP) and the peritubular capillary reabsorptive coefficient (LpAR) (APR = ERP . LpAR). The ERP is defined by the net hydrostatic and oncotic pressure gradient acting across the capillary wall from interstitium to peritubular capillary flow. The relationship APR = ERP . LpAR is predefined, and steady-state measurements do not permit determination of causality because primary changes in any variable obligate a proportional change in a second variable. As an example of the difficulties in interpretation of this type of analysis, we have examined the APR and factors contributing to ERP and LpAR before and after the administration of benzolamide, a carbonic anhydrase inhibitor, to saline-expanded Munich-Wistar rats. Alterations in peritubular capillary fluid uptake cannot always be interpreted as casual mechanisms for changes in absolute fluid reabsorption but may result from primary alterations in epithelial transport.
Effect of osmolarity on cation fluxes in medullary thick ascending limb cells
Authors: Eveloff J. L. , Calamia J.
Published: December 2017

The effects of a hypertonic extracellular medium on furosemide-sensitive Na and K fluxes were studied in isolated cells from the rabbit medullary thick ascending limb of Henle's loop (mTALH). In the control incubation medium, the furosemide-sensitive 22Na uptake was 379.1 +/- 24.4 pmol . mg protein-1 . min-1 and the furosemide-sensitive 86Rb uptake was 30.5 +/- 16.9. The furosemide-sensitive 22Na flux was not stimulated by K gradients directed into the cells, and, conversely, the furosemide-sensitive 86Rb flux was not stimulated by Na gradients directed into the cells. These findings are consistent with a Na-Cl cotransport system. In the presence of 200 mM mannitol, the furosemide-sensitive 22Na and 86Rb fluxes were increased dramatically to 919.4 +/- 76.6 and 106.1 +/- 29.2 pmol . mg protein-1 . min-1, respectively. When the osmolarity of the incubation medium was increased, not only were the furosemide-sensitive fluxes increased but these fluxes became inter-dependent, i.e., removing Na or K prevented the increase in the furosemide-sensitive flux of the other cation. This finding is consistent with a Na-K-2Cl cotransport system in the mTALH cells. The data suggest that the Na-Cl and the Na-K-2Cl cotransport systems may be distinct functions of the same furosemide-sensitive cotransport system and that their expression may be regulated by changes in cell volume.
Atriopeptin III increases cGMP in glomeruli but not in proximal tubules of dog kidney
Authors: Stokes T. J. , McConkey C. L. , Martin K. J.
Published: December 2017

Atriopeptin III is natriuretic, diuretic, and phosphaturic in the intact dog and relaxes vascular and nonvascular smooth muscle in vitro. The mechanism of the renal effects of atriopeptin remains ill defined but may include hemodynamic alterations and/or direct tubular effects. Since many peptide hormones act through changes in cyclic nucleotide formation, we examined the effect of synthetic atriopeptins on cAMP and cGMP accumulation in isolated glomeruli and proximal tubules from normal dog kidney. Synthetic atriopeptin produced a dose-related increase in cGMP in glomeruli with a Kact of 200 +/- 19 nM and a maximal activity of 64.1 +/- 6.3 pmol cGMP X mg prot-1 X 5 min-1. In the presence of 4 mM Mn2+ Kact was reduced to 19 +/- 2 nM with no change in maximal cGMP production (66.2 +/- 11.8 pmol cGMP X mg prot-1 X 5 min-1). Atriopeptin (1 microM) did not increase cGMP accumulation above basal levels in proximal tubule segments. The cAMP production of neither glomeruli nor proximal tubules was stimulated by atriopeptin. These studies demonstrate a dose-dependent stimulation of guanylate cyclase by atriopeptin in glomeruli but not in proximal tubule segments. In addition, atriopeptin neither stimulates nor inhibits cAMP accumulation in glomeruli or proximal tubules. These data suggest a major role for the renal effects of atriopeptin at the glomerular level, possibly through hemodynamic effects or changes in the glomerular ultrafiltration coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)
Alteration of chloride secretion across canine tracheal epithelium by lipoxygenase products of arachidonic acid
Authors: Leikauf G. D. , Ueki I. F. , Widdicombe J. H. , Nadel J. A.
Published: December 2017

We examined whether the leukotrienes (LT) B4, C4, D4, and E4, and 5-, 12-, and 15-hydroxyeicosatetraenoic (HETE) acids alter the electrical properties of canine tracheal epithelium. Short-circuit current (ISC) increased by 20.3 +/- 4.3 and 25.9 +/- 6.5 microA/cm2 after LTC4 and LTD4 addition, was unchanged following LTB4, LTE4, 5-, or 15-HETE addition, and was decreased by 10 +/- 3% after 12-HETE addition. LTC4- and LTD4-induced increases in ISC were dependent on the presence of Cl and were equal to the increases in net 36Cl flux toward the mucosa. The cyclooxygenase inhibitor indomethacin (10(-5) M) or the phospholipase inhibitor mepacrine (10(-5) M) diminished increases in ISC. The release rate of prostaglandins E2 and F2 alpha and thromboxane B2 rose from 8.2 +/- 2.3, 2.3 +/- 0.5, and 1.1 +/- 0.5 to 15.5 +/- 3.3, 6.0 +/- 1.4, and 4.0 +/- 0.8 ng . cm-2 . h-1, respectively, after LTC4 addition, and from 6.9 +/- 1.4, 2.5 +/- 1.1, and 1.7 +/- 1.3 to 20.2 +/- 3.1, 10.5 +/- 3.1, and 5.2 +/- 2.4 ng . cm-2 . h-1, respectively, after LTD4 addition. The release rates of 6-keto-prostaglandin F1 alpha were unchanged. A thromboxane A2 mimetic, U46619, failed to increase ISC and thromboxane synthetase inhibitors OKY-046 and dazmegrel failed to inhibit the induced increases in ISC, suggesting that thromboxane has little effect on ISC. Thus lipoxygenase products of arachidonic acid can modulate Cl secretion by the canine tracheal epithelium and do so through the release of cyclooxygenase products, including prostaglandins E2 and F2 alpha.
Effect of indomethacin on papillary solute concentration in the potassium-deficient rat
Authors: Takamitsu Y. , Kunau R. T.
Published: December 2017

Administration of indomethacin or meclofenamate to normal rats increases renal papillary solute concentration primarily by enhancing solute addition. A reduction in papillary solute concentration is characteristic of potassium deficiency. Of the multiple factors probably responsible for this reduction, several can be influenced by indomethacin or meclofenamate. The present study examined the effect of indomethacin on papillary solute concentration in the potassium-deficient rat. Indomethacin increased papillary solute concentration in normal but not potassium-deficient rats when studied in the conscious hydropenic state. Since indomethacin could increase papillary plasma flow in the potassium-deficient rat, potentially negating any enhancement of solute transport into the papilla, papillary plasma flow and papillary Cl concentration were determined in anesthetized surgically manipulated rats. Base-line papillary Cl concentrations were reduced in this setting. Indomethacin increased papillary plasma flow only in potassium-deficient rats but increased papillary Cl concentration equivalently in normal and potassium-deficient rats. The ability of indomethacin to increase papillary solute concentration in the potassium-deficient rat seemingly depends upon the experimental setting.
Transport of solute in proximal tubules is modified by changes in medium osmolality
Authors: Williams J. C. , Barfuss D. W. , Schafer J. A.
Published: December 2017

To examine the hypothesis that fluid absorption is driven by transepithelial osmotic differences, we measured such differences in proximal tubules perfused under oil and attempted to increase the rate of fluid absorption (Jv) and hence the absorbate-perfusate osmotic differences by lowering the osmolality of the perfusate. We were able to consistently increase Jv in this manner only in proximal straight tubules perfused with a simple perfusate that contained no bicarbonate or amino acids. With the simple perfusate, a small but significant increase in the absorbate-perfusate osmolality difference was seen with increased Jv, which is expected if the volume absorption is driven by a transepithelial osmotic difference. In addition, lowering the perfusate osmolality from 290 to 160 mosmol/kg H2O increased the rate of solute absorption from 79 +/- 7 to 91 +/- 8 posmol . min-1 . mm-1; this increase was partly accounted for by an increase in the rate of absorption of glucose from 6.6 +/- 0.9 to 9.5 +/- 1.1 pmol . min-1 . mm-1. In contrast, with the complete perfusate in proximal straight tubules there was little or no increment in Jv, no change in transepithelial osmolality differences, and a decrease in the rate of solute transport with hypoosmolality from 136 +/- 21 to 87 +/- 22 posmol . min-1 . mm-1. In proximal convoluted tubules, similar results were obtained, but a time-dependent decline of Jv complicated the interpretation of the results in the convoluted tubules. It is hypothesized that the observed changes in solute transport with hypotonic perfusate may be the result of changes in membrane permeability that are subsequent to cell swelling.
Frequency domain analysis of renal autoregulation in the rat
Authors: Sakai T. , Hallman E. , Marsh D. J.
Published: December 2017

The frequency response of renal blood flow was estimated to test our suggestion that autoregulation had one fast and one slow component. Arterial pressure was varied periodically by a pump connected to the distal aorta or aperiodically by stimulating atrial fibrillation. There was only one regulatory mechanism, corresponding to the slow component seen earlier. Two apparent regulators were seen when pressure was measured far from the renal artery (right common carotid), rather than near (superior mesenteric). Simultaneous measurements of pressure in both arteries showed interference of the pressure wave from the heart with pressure waves from the pump in the distal aorta at frequencies near that of the heart rate. Measurements made in the superior mesenteric artery were likely to be correct. The earlier results were in error, and frequency response methods detect only one regulator. Animals made acutely hypertensive behaved similarly. The effect of the regulator appears as a phase shift at frequencies of 0.25 Hz and below and an attenuated flow magnitude at frequencies below 0.1 Hz. This frequency response is consistent with the flow propagation time to the macula densa. We conclude that macula densa feedback was the only flow-regulating mechanism detected.
Inhibition of Ca absorptive flux by chlorthalidone in the rat duodenum and colon
Authors: Gafter U. , Lau K. , Garno J. , Kathpalia S.
Published: December 2017

To evaluate the mode and intestinal sites of action of chlorthalidone on Ca transport, balance and flux studies by the Ussing technique were performed in rats fed a low Ca diet throughout the experiment to stimulate Ca absorption. Half of the rats received chlorthalidone (5 mg X kg-1 X day-1) orally for 18 wk, a duration of administration previously shown to yield consistent changes. Net Ca absorption was decreased by chlorthalidone (0.91 +/- 0.07 vs. 1.08 +/- 0.3 mg/day, P less than 0.05), which is similar to prior observations in rats fed a normal Ca diet. Ca balance was unchanged by chlorthalidone (0.34 +/- 0.08 vs. 0.36 +/- 0.05 mg/day) because of concomitant hypocalciuria of similar magnitudes. In the duodenum, chlorthalidone decreased mucosal-to-serosal flux (Jm----s) (96.7 vs. 111.5 nmol X cm-2 X h-1, P less than 0.05). Since serosal-to-mucosal flux (Js----m) was unchanged, net Ca flux (Jnet) was reduced (74.0 vs. 89.6 nmol X cm-2 X h-1, P less than 0.05). Similarly, chlorthalidone selectively inhibited Jm----s in the descending colon (27.0 vs. 36.2 nmol X cm-2 X h-1, P less than 0.01), reducing Jnet (14.3 vs. 23.2 nmol X cm-2 X h-1, P less than 0.005). Short-circuit current and tissue conductance were unaffected. These data suggest that chronic chlorthalidone treatment reduces Ca absorption by inhibiting active calcium transport in the small and large intestine.
Functional heterogeneity in the early distal tubule of the Amphiuma kidney: evidence for two modes of Cl- and K+ transport across the basolateral cell membrane
Authors: Guggino W. B.
Published: December 2017

Measurements of cell volume and basolateral cell membrane potential difference (Vbl) were made simultaneously and on the same cell to study chloride and potassium transport across the basolateral cell membrane of individual cells from the Amphiuma early distal tubule or diluting segment. Two distinct types of responses of Vbl are evident when either chloride is lowered or potassium is raised in the basolateral solution. In one cell type (high basolateral conductance, HBC), these maneuvers cause large depolarizations in Vbl, suggesting that the basolateral cell membrane has significant partial conductances to both chloride and to potassium. In contrast, Vbl of another group (low basolateral conductance, LBC) is much less sensitive to the same maneuvers, indicating that the partial conductance of the basolateral cell membrane is quite low. Consistent with the difference in partial conductance is the ratio of resistances, which is immeasurably high in HBC cells and averages 1.2 +/- 0.4 in LBC cells. Increasing basolateral potassium to 98 mM causes both types to swell, with HBC cells swelling approximately two times faster than LBC cells. In both cell types, potassium-induced cell swelling is inhibited by removing chloride from the perfusion solutions. In animals kept in a low-potassium environment, the number of HBC cells is approximately equal to the number of LBC cells. The proportion of LBC cells increases following potassium adaptation. This data suggests that there are at least two types of cells present in Amphiuma early distal tubule, one cell type in which both chloride and potassium move across the basolateral cell membrane primarily via a conductive pathway and another in which the movements are mostly electroneutral, probably involving a K-Cl cotransport system, and that this heterogeneity may change in response to the metabolic state of the animal.
Stoichiometry of sodium chloride transport by rectal gland of Squalus acanthias
Authors: Silva P. , Myers M. A.
Published: December 2017

The stoichiometry of the sodium chloride cotransport system was examined in isolated perfused rectal glands of Squalus acanthias by kinetic analysis of the effect on chloride secretion of progressive substitutions of other ions for sodium and chloride in the perfusate. Secretion was stimulated by a constant infusion of dibutyryl cyclic AMP (5 X 10(-5) M) and theophylline (2.5 X 10(-4) M). Sodium was replaced by N-methyl-D-glucamine, whereas chloride was replaced by gluconate. The Km values for sodium, obtained using three different graphic methods, were close to or at the normal concentration of sodium in the plasma of the shark, suggesting that plasma sodium concentration regulates transport by the gland. The Km values for chloride were far below the normal concentration of chloride in the plasma, indicating that the chloride sites are normally saturated and therefore plasma chloride concentration cannot control transport by the gland. Hill plots revealed slopes of 1.06 for sodium and 1.6 for chloride, consistent with the hypothesis that 2 Cl- and 1 Na+ interact in the cotransport process. The cotransport linkage of 2 Cl- with 1 Na+ in the initial step of entry into the cell can be viewed as a device that doubles the energetic efficiency of salt transport, allowing 2 NaCl to be secreted for every 1 Na+ actively pumped.
Relationship between renal hemodynamic and natriuretic effects of atrial natriuretic factor
Authors: Sosa R. E. , Volpe M. , Marion D. N. , Atlas S. A. , Laragh J. H. , Vaughan E. D. , Maack T.
Published: December 2017

The degree by which atrial natriuretic factor (ANF)-induced renal hemodynamic changes account for its natriuretic effect was determined by early clamp experiments in six anesthetized dogs. After control periods, perfusion pressure of the left kidney (LK) was reduced to 80-90 mmHg, and synthetic ANF (auriculin A) was infused intravenously (0.3 micrograms X min-1 X kg body wt). After recovery, furosemide (F) was administered as a bolus injection (1 mg/kg body wt). In the right kidney (RK), which served as a time control, ANF increased (P less than 0.05) glomerular filtration rate (GFR) 16 +/- 4% and Na excretion (UNa V) 261 +/- 63%, whereas it decreased urine osmolality (Uosm) 36 +/- 7% without changing free water clearance. ANF also increased diuresis (V) and kaliuresis (UKV). F produced qualitatively the same results without changing GFR. In the clamped LK, ANF failed to increase GFR (22 +/- 4 vs. 26 +/- 4 ml/min), UNaV (30 +/- 9 vs. 33 +/- 11 mueq/min), V, and UKV or to decrease Uosm (841 +/- 97 vs. 840 +/- 114 mosmol/kg H2O). F had similar effects in LK as in RK. The data demonstrate that the natriuretic effect of ANF is abolished when its renal hemodynamic actions are impeded. In addition, the results demonstrate that ANF antagonizes renal vasoconstriction in the dog. The results are consistent with the view that the ANF-induced natriuresis is due in great part to an increase in the filtered load of Na into a washed-out inner medulla.
Role of calcium in pathogenesis of acute renal failure
Authors: Humes H. D.
Published: December 2017

The potential for calcium to play a key role in cell injury has been long suspected. Major sites of calcium action to promote cell injury include the plasma membrane, mitochondria, endoplasmic reticulum, and the cytoskeleton. Major mechanisms of calcium action to promote cell injury include activation of phospholipases, direct and indirect effects on permeability pathways, and effects on contractile and cytoskeletal structure and function. The activation of phospholipases and deterioration of mitochondrial structure and function by calcium appear to be most important in the evolution of cell injury. Tissue calcium levels invariably increase when lethal cell injury develops in a tissue and is due predominantly to mitochondrial accumulation and sequestration. The simultaneous occurrence of cell calcium overload and lethal cell injury, however, only establishes an association between these two events but does not prove causality. Over the past several years, a large amount of data has established that calcium plays a critical modifying role in the pathogenesis of both ischemic and toxic cell injury, but evidence for the thesis that calcium is the “final common pathway” for lethal cell injury is not conclusive. Many studies have emphasized the role of calcium influx from extracellular to intracellular spaces with resulting cellular calcium overload in cell injury. A critical role for intracellular redistribution of calcium pools rather than cellular calcium influx during the important early stages of cell injury may be more important. Modifying alterations in cell calcium redistribution or cellular calcium influx with a variety of agents has been beneficial in ameliorating the degree of cell injury in a number of experimental settings. It is still unclear whether these beneficial effects are due mainly to alterations of calcium-mediated processes that determine the reversibility of injury or are due to alterations in other critical metabolic processes not importantly influenced by calcium.
Electrolyte handling by the superficial nephron of the rabbit
Authors: Wong N. L. , Whiting S. J. , Mizgala C. L. , Quamme G. A.
Published: December 2017

A micropuncture study of the rabbit was performed to evaluate the function of the superficial nephron. The mean glomerular filtration rate of the left micropunctured kidney was 4.0 +/- 0.8 ml/min. The concentration profile of electrolytes within the proximal tubule was similar to that of species previously investigated except for potassium. The mean tubular fluid (TF)-ultrafilterable (UF) concentration ratios were as follows: sodium, 1.01 +/- 0.03; chloride, 1.14 +/- 0.04; calcium, 1.12 +/- 0.04; magnesium, 1.47 +/- 0.08; and phosphate, 0.94 +/- 0.09, with a mean TF-plasma (P) inulin concentration ratio of 1.78 +/- 0.14 (n = 32). The TF/UF potassium value significantly increased in association with TF/P inulin to a mean value of 1.26 +/- 0.06. Accordingly, 29% of the filtered potassium was reabsorbed in the superficial proximal tubule compared with 43% of the filtered sodium. The loop of Henle reabsorbed 55-60% of the filtered sodium, chloride, and calcium, whereas considerably less magnesium (33%) was reabsorbed. Segments beyond the distal tubule collection site reabsorbed little of the delivered magnesium, which supports the notion that the loop of Henle is the principal segment accounting for adjustments in magnesium balance. These studies indicate that the superficial nephron of the rabbit performs similar to other species reported, except potassium reabsorption is significantly less in the proximal convoluted tubule.
Ascorbic acid transport in mammalian kidney
Authors: Rose R. C.
Published: December 2017

Ascorbic acid is known to circulate free in the plasma of several species and is therefore filtered in the kidney; reabsorption subsequently takes place and prevents urinary loss. However, no specific mechanism of renal ascorbic acid transport has previously been presented. In the present study, rat and guinea pig kidney were incubated as slices or as isolated tubules in vitro in the presence of low concentrations of [14C]ascorbic acid. The kidneys of both species handle ascorbic acid similarly. Ascorbic acid accumulates in the renal tissue to a concentration three to four times that present in the bathing media. Recently absorbed ascorbic acid diffuses freely from the kidney and is predominantly nonmetabolized during absorption. Uptake is reduced following replacement of bathing solution sodium by lithium or cesium, or when incubation is performed in the presence of metabolic inhibitors or at low temperatures. The results indicate that ascorbic acid is reabsorbed in the kidney by a sodium-dependent active transport mechanism that operates by concentrating ascorbic acid in the cellular fluid. Renal slices and tubules both appear to transport ascorbic acid and galactose across the brush-border membrane; this indicates that the tubular lumens in these preparations are not collapsed or sealed off.