bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of renal prostaglandins to the natriuretic action of bradykinin in the dog
Authors: Blasingham M. C. , Nasjletti A.
Published: December 2017

To study the effects of stimulation of renal prostaglandin biosynthesis by bradykinin, we assessed the changes in renal functions induced by intrarenal infusion of bradykinin (10 ng . min-1 . kg-1) in the dog anesthetized with pentobarbital before and during inhibition of prostaglandin synthesis by sodium meclofenamate (5 mg/kg). Before meclofenamate administration, bradykinin augmented the urinary output of a "PGE"-like substance from 1.00 +/- 0.25 to 3.88 +/- 1.09 ng/min (P less than 0.05) and increased renal blood flow by 65 +/- 9 ml/min (P less than 0.001), urine flow by 0.55 +/- 0.23 ml/min (P less than 0.05), and sodium excretion by 64.8 +/- 18.0 mueq/min (P less than 0.01). Administration of meclofenamate did not affect the bradykinin-induced increase in renal blood flow and urine volume, but suppressed the evoked output of "PGE" and reduced the associated natriuresis, i.e., sodium excretion increased by only 11.1 +/- 4.8 mueq/min (P greater than 0.05). In contrast, meclofenamate did not affect the natriuresis effected by an equidilator dose of PGE2 (5 ng . min-1 . kg-1) infused intrarenally. These observations suggest that a product of prostaglandin synthetase produced by the kidney during intrarenal infusion of bradykinin contributes to the natriuretic action of the peptide.
Effects of lumen volume transit time and pressure on loop of Henle function
Authors: Baines A. D. , Basmadjian D. , Wang B. C.
Published: December 2017

Experiments on Henle's loops were designed to demonstrate the relationships of absorption to distal pressure, transit time, and luminal diameter. Loops of superficial nephrons in hydropenic rats, isolated from the rest of the nephron by oil or solid paraffin blocks, were microperfused at 13.6--20 nl/min. Two samples of fluid were collected from the early distal tubule--one with suction in order to lower distal pressure and reduce luminal volume, the other without suction so that the lumen was distended. Transit times were 30 +/- 2 s without and 19 +/- 2 s with suction. Proximal tubule pressure and perfusion rate were not altered by collection with suction. Absolute absorption, however, descreased from 10.6 +/- 0.4 to 8.4 +/- 0.4 nl/min (P less than 0.001). When salt transport was inhibited by 10(-4) M furosemide in the perfusate, water absorption was 7.8 +/- 0.7 nl/min without suction and 6.1 +/- 0.8 nl/min with suction (P less than 0.01). Computer simulation of Henle's loop shows that these observations cannot be explained by changes in transit time, hydrostatic pressure, or unstirred layers. The observations are simulated when radial fluxes depend on wall thickness and surface area in the descending thin limb.
Dissociation between plasma, urine, and renal papillary cyclic AMP content following vasopressin and DDAVP
Authors: Bia M. J. , Dewitt S. , Forrest J. N.
Published: December 2017

The effects of in vivo physiologic doses of vasopressin and 1-deamino-8-D-arginine vasopressin (DDAVP) on the cyclic AMP content of plasma, urine, and renal papillary tissue were determined in the ADH-deficient Brattleboro rat. During clearance studies, plasma cyclic AMP concentrations and both total and nephrogenous urinary cyclic AMP excretion in vasopressin- and DDAVP-treated rats were similar to the values in time-matched controls. In contrast, in situ renal papillary cyclic AMP content was higher (P less than 0.001) in both vasopressin- (35.7 +/- 3.6 pmol/mg protein) and DDAVP- (29.7 +/- 2.2 pmol/mg protein) treated rats compared to controls (15.1 +/- 1.3 pmol/mg protein). Endogenous stimulation of vasopressin by dehydration in normal rats increased both papillary cyclic AMP content (27.1 +/- 2.7 pmol/mg protein) and urine osmolality, whereas no change in papillary cyclic AMP was observed following dehydration in Brattleboro rats (13.6 +/- 0.8 pmol/mg protein) despite an increase in urine osmolality. The results demonstrate that changes in cyclic AMP following in vivo vasopressin are best demonstrated by measurement of in situ cyclic AMP content of the renal papilla, whereas total urinary cyclic AMP and nephrogenous cyclic AMP are not useful indices of tubular sensitivity to this hormone.
Proximal tubular response to variations in extracellular sodium concentration
Authors: Corman B. , Carriere S. , Le Grimellec C. , Cardinal J.
Published: December 2017

In vitro microperfusion was used to study the effect of low and high extracellular sodium concentrations on the transport capacity of the proximal convoluted tubule (PCT). Tubules from rabbit kidney were perfused with luminal and peritubular solutions containing 80, 115, 190, and 225 mM sodium. Control solutions contained 150 mM sodium. No ionic substitution was made and the proximal convoluted tubules were studied under hypo- or hypertonic conditions after a 20-min equilibration period. Sodium concentration was measured at 80, 150, and 225 mM sodium in the perfused and collected fluids and no significant difference was observed. Net sodium transport (JNa) remained relatively constant between 115 and 150 mM sodium. It decreased progressively at high sodium concentrations. Depression in JNa was also observed at 80 mM sodium. Fractional sodium reabsorption increased to 125.0% of control at 115 mM sodium and decreased to 69.4 and 40.1% at 190 and 225 mM sodium, respectively. At 80 mM, the results were not different from control. These findings indicate that at concentrations of 115-225 mM sodium the proximal convoluted tubule has the intrinsic capacity to regulate sodium transport.
Parathyroid hormone metabolism and its potential as a uremic toxin
Authors: Slatopolsky E. , Martin K. , Hruska K.
Published: December 2017

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a “uremic toxin” responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant “uremic toxin.”
Comparison of micropuncture and microcatheterization in papillary collecting duct
Authors: Sonnenberg H. , Chong C.
Published: December 2017

Collecting duct transport of fluid, sodium, and potassium was studied in rats infused with Ringer solution (5 ml·100 g body wt-1·h-1). A terminal segment of surface collecting duct in the exposed papilla was catheterized as far upstream as possible under visual observation. After fluid sampling the same duct was punctured at the same site with a glass micropipette and a second sample was taken. Samples were then obtained from the opening of the duct at the papilla tip by both catheter and micropipette. No significant difference between the two collection sites was found in the fraction of filtered sodium, potassium, or fluid remaining in the tubule, independent of the sampling technique used, indicating that volume expansion inhibited salt and water reabsorption. Although fractional fluid and sodium remainders were slightly higher and potassium remainder lower in upstream micropuncture samples compared to catheterization samples, the good correlation between collections obtained with both techniques suggests that both are equally valid as indicators of transport in terminal collecting ducts.

Ringers infusion; extracellular fluid volume expansion; fluid reabsorption; sodium and potassium transport

Submitted on May 7, 1979

Accepted on January 22, 1980
Micropuncture study of tubular transport of urate and PAH in the pig kidney
Authors: Roch-Ramel F. , White F. , Vowles L. , Simmonds H. A. , Cameron J. S.
Published: December 2017

At physiological plasma urate concentration (Purate) (0.05 mg/dl), net secretion of urate occurred in the convoluted part of the proximal tubule of micropunctured anesthetized pigs. The fraction of filtered urate delivered to the point of micropuncture ((TF/P)urate/(TF/P)polyfructosan) was 4.8 +/- 0.5 (mean +/- SE, n =10). Urate was reabsorbed from lower tubular segments, since the fractional excretion of urate (FEurate) was only 2.1. Saturation of secretion as well as reabsorption occurred at Purate of 1.6 mg/dl. p-Aminohippurate (PAH) secretion also occurred mainly in the pars convoluta of the proximal tubule: (TF/P)PAH/(TF/P)polyfructosan was 4.0 +/- 0.4 (n = 11), whereas the FEPAH was 4.5 +/- 0.5 (n = 5). Thus, the pars recta does not contribute significantly to the net secretion of either urate or PAH. PAH was a competitive inhibitor of urate secretion. At a PPAH of 60 mg/dl there was overall net reabsorption of urate. Accordingly, in the pig PAH and urate seem to be secreted by the same transport mechanism.
Renal responses to central vascular expansion are suppressed at night in conscious primates
Authors: Kass David A. , Sulzman Frank M. , Fuller Charles A. , Moore-Ede Martin C.
Published: December 2017

Renal and hemodynamic responses to central vascular volume expansion induced by 4 h of continuous lower bodv positive air pressure (LBPP) were examined in conscious, chair-restrained squirrel monkeys in a light/dark (12:12) cycle. LBPP (30 mmHg) during both day (1200–1600) and night (0000–0400) induced similar 4 cmH2O stable increases in central venous pressure (P < 0.001), rises in heart rate of 25 beat/min (P < 0.001), and small transient elevations in mean arterial blood pressure. In contrast, while daytime LBPP induced a significant increase in urine flow (V) from 2.12 ± 0.31 to 3.5 ± 0.42 ml/h (P < 0.05), and sodium excretion (UNaV) from 71.1 ± 14 to 271.2 ± 37 μeq/h (P < 0.001), there was a marked nocturnal inhibition of the response to LBPP, with no significant increases in V or UNaV. Urine osmolality decreased by more than 50% at both times of pressure exposure; potassium excretion was not significantly affected by either exposure, and drinking was suppressed during daytime LBPP. Comparisons of the time course and diurnal regulation of the urinary responses suggest that several separate efferent control pathways are involved.

volume regulation; sodium excretion; squirrel monkey (Saimiri sciureus); lower body positive air pressure; circadian rhythms; Henry-Gauer reflex

Submitted on October 29, 1979

Accepted on April 10, 1980
Stimulation of ammoniagenesis by acute acidosis: evidence for a urinary inhibitor
Authors: Terao N. , Tannen R. L.
Published: December 2017

To elucidate the factors mediating the response of renal ammoniagenesis to acute acidosis, the isolated perfused rat kidney was subjected to acute metabolic and respiratory acidosis with either standard collection or drainage of urine back into the perfusate. Midway during a 90-min perfusion with 0.4 mM glutamine and 5 mM glucose, perfusate pH was decreased to 6.8 by addition of HCl or alteration of the PCO2. Metabolic acidosis increased NH3 production, acidified the urine, and increased urinary NH4 excretion. Respiratory acidosis increased NH3 production to a comparable degree without urine acidification and with a minimal increase in NH4 excretion. When respiratory acidosis preceded perfusion at control PCO2 levels, NH3 production was increased but NH4 excretion was lower than control values. If urine drained back into the perfusate, NH3 production was not altered by either metabolic or respiratory acidosis. Accordingly, acute changes in perfusate pH stimulate renal ammoniagenesis by the isolated perfusate pH stimulate renal ammoniagenesis by the isolated perfused kidney independent of changes in urinary pH and NH4 excretion. This response is inhibited by an unidentified factor excreted in the urine.
Effects of PTH, ADH, and cyclic AMP on distal tubular Ca and Na reabsorption
Authors: Costanzo L. S. , Windhager E. E.
Published: December 2017

Tubular microperfusion experiments were performed in rats to examine the effects of thyroparathyroidectomy (TPTX), parathyroid hormone (PTH), antidiuretic hormone (ADH), and cyclic AMP (cAMP) on distal tubular Ca, Na, and water reabsorption. TPTX caused a significant decrease in the Ca reabsorptive rate as compared to intact animals. PTH (5 U/kg; 2 U x kg-1 x h-1) replacement in TPTX animals restored Ca transport to control levels. Application of either cAMP (10(-3) M) or 8-(p-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (10(-5) M) to the surface of the kidney caused a stimulation of Ca reabsorption similar to that produced by PTH. Neither TPTX nor PTH changed Na or water reabsorption significantly, whereas the cyclic nucleotides increased both of these parameters. These later actions of cAMP duplicated effects of ADH observed in these distal tubules.
Lactate-sodium cotransport in rat renal brush border membranes
Authors: Barac-Nieto M. , Murer H. , Kinne R.
Published: December 2017

Brush border membrane vesicles were obtained from rat kidney cortex through a calcium precipitation method and their transport properties for lactate were studied by a rapid-filtration technique. Transient concentrative uptake of L-lactate was observed in the presence of inwardly directed NaCl gradient, but not in the presence of a KCl, LiCl, RbCl, CsCl, or choline chloride gradient. The sodium-dependent L-lactate uptake was saturable and was inhibited by D-lactate. The activation curve with sodium was hyperbolic. Maneuvers that render the inside of the vesicle more negative stimulated sodium-dependent L-lactate uptake, suggesting an electrogenic transfer of L-lactate and sodium. An L-lactate gradient also accelerates the sodium movement across the brush border membrane. Studies on the pH dependency of L-lactate transport and on the effect of L-lactate on proton movements across the brush border membrane indicate that there is little contribution of nonionic diffusion and/or of lactate-H+ cotransport to the transfer of L-lactate across the renal brush border membrane. In summary, sodium-lactate cotransport is the major mechanism for L-lactate transfer across the renal brush border membrane.
Mechanisms and classification of deranged distal urinary acidification
Authors: Arruda J. A. , Kurtzman N. A.
Published: December 2017

Distal renal tubular acidosis has been thought to be the consequence of an impaired ability to maintain a large pH gradient between distal nephron urine and blood. Recent evidence suggests that the classification of deranged distal nephron acidification requires expansion. These mechanisms whereby the urine is acidified in the distal nephron include an active component, a passive component, and a component of bicarbonate secretion. Active proton secretion is influenced by the integrity of the pump and the nature of the electrical chemical gradient against which it operates. The passive component relates either to the backleak of acid from lumen to blood or the leak of bicarbonate from blood to lumen; under ordinary circumstances this passive component is negligible. Aldosterone also influences distal acidification. A defect in most of these components can be identified experimentally. We propose a classification of deranged distal acidification that will allow identification of the mechanism responsible for the defect. This classification, which employs measurement of the urinary carbon dioxide gradient, the response of the kidney to sulfate or phosphate administration, the urinary pH during acidosis, and the state of potassium and sodium excretion, can easily be performed in human subjects.
Acute effect of calcitonin on rat renal electrolyte transport
Authors: Carney S. , Thompson L.
Published: December 2017

Renal clearance studies were performed on parathyroid-intact and acutely thyroparathyroidectomized (TPTX) rats to clarify calcitonin (CT) action on renal electrolyte transport. Although CT (0.15 U x 100 g body wt-1 x h-1) reduced fractional excretion of calcium and magnesium by 72 and 46%, respectively, in TPTX rats without altering sodium and phosphate excretion, a 10-fold increase in CT (1.5 U) caused a smaller reduction in calcium and magnesium excretion and significantly increased sodium and phosphate excretion. A higher CT dose (15 U) did not alter calcium excretion, increased magnesium excretion, and caused an even greater increase in sodium and phosphate excretion. Results in parathyroid-intact animals were similar. Despite the fall in plasma calcium following CT administration, the filtered calcium load was unaltered due to a concomitant increase in glomerular filtration rate. Calcium infusion prior to CT (0.15 U) prevented a detectable fall in plasma calcium concentration. However, a 45% fall in fractional calcium excretion occurred despite the significant increase in filtered calcium. These data suggest that the physiological role of calcitonin on the nephron is to conserve calcium. Reports of increased electrolyte excretion presumably reflect a depressant effect of pharmacological doses of CT on nephron function.
Thromboxane B2 and prostaglandin E2 in the K+-depleted rat kidney
Authors: Beck N. , Shaw J. O.
Published: December 2017

There is a considerable amount of interest in prostaglandin E2 (PGE2) metabolism in potassium depletion, but the findings remain inconclusive. Thromboxane A2 (TXA2) is another type of prostaglandin with a vasoconstrictive property and its biosynthesis in the kidney is altered under pathophysiological conditions. We investigated the production of both immunoassayable PGE2 and thromboxane B2 (TXB2), a chemically stable metabolite of TXA2, in the chronically K+-depleted rat kidney. During a 90-min in vitro incubation of papillary slices obtained from K+-depleted rats, TXB2 production was increased, but PGE2 biosynthesis was decreased and PGF2 alpha remained unaltered compared with control rats. In the cortex, TXB2 production was low, but it was greater in K+-depleted rats compared with control rats. Deletion of K+ from the incubation medium had no measurable effect on either TXB2 or PGE2 production in both K+-depleted and control rats. Formation of [14C]TXB2 from [14C]PGH2 by microsomes from renal papilla was greater in K+-depleted rats compared with control rats, suggesting that the increased TXB2 production in the K+-depleted rat kidney is probably due to an activation of TXA2 synthetase.
Circulating catecholamines in control of renal electrolyte and water excretion
Authors: Johnson M. D. , Barger A. C.
Published: December 2017

Graded physiological doses of norepinephrine or epinephrine were infused either intravenously or directly into the renal artery of conscious dogs previously prepared with chronic indwelling catheters. Infusion rates ranged from 5 to 125 ng . kg-1 . min-1, and aortic plasma catecholamine concentrations were measured during intravenous infusion to determine the actual levels achieved. Even when the renal arterial plasma norepinephrine concentration was raised to 5,000 pg/ml by either intravenous or intrarenal infusion, only a modest sodium and potassium retention was observed. Only intravenous norepinephrine increased urinary flow rate. Increments of epinephrine concentration from 120 to 2,000 pg/ml decreased sodium and potassium excretion only when delivered intravenously. The concentrations of norepinephrine or epinephrine required to alter urinary sodium and potassium excretion and flow rate were in the upper physiological range or higher and the responses were small except for intravenous epinephrine, which decreased sodium excretion at very low physiological concentrations (120-400 pg/ml). We conclude that circulating epinephrine may play an important physiological role in renal sodium conservation. This effect of epinephrine is not due to a direct intrarenal mechanism.
Removal and excretion of immunoreactive rat growth hormone by the isolated kidney
Authors: Rabkin R. , Gottheiner T. I. , Fang V. S.
Published: December 2017

The renal uptake of immunoreactive rat growth hormone (rGH), molecular weight 21,500 daltons, was examined in the isolated perfused rat kidney to determine whether peritubular removal of a protein greater than 12,000 daltons occurs and to assess the functional characteristics of renal GH uptake. Organ clearance of rGH (OCGH) in control kidneys was 1,039 +/- 99 microliters/min and was unaffected by an excess of insulin but markedly depressed by col (10 degrees C( and KCN. Although glomerular filtration rate (GFR) did not differ significantly from OCGH in the control rats, we suspected that filtration could not account for all the rGH removed because of glomerular protein sieving. However, GFR was significantly less than OCGH with cold and KCN treatment, indicating the occurrence of peritubular removal. In nonfiltering kidneys, rGH removal exceeded that of [14C]inulin (P less than 0.05), demonstrating peritubular rGH removal. Tubular absorption of rGH was unaffected by insulin but markedly depressed by cold and KCN. We conclude that rGH is removed from the renal circulation mainly by the glomerular filtration-tubular absorptive pathway, but, in addition, as with smaller proteins, that peritubular removal occurs.
Effect of glucagon on zinc excretion in anesthetized dogs
Authors: Victery W. , Levenson R. , Vander A. J.
Published: December 2017

The present studies were performed on anesthetized dogs to determine whether urinary zinc excretion is altered when plasma glucagon concentration is elevated acutely. Glucagon infusion (5 ng.kg-1.min-1) adequate to double base-line plasma glucagon significantly increased zinc excretion in a reversible manner; plasma zinc concentration was unchanged. A larger dose of glucagon (50 ng.kg-1.min-1) produced no significantly greater effect. Clearance experiments using 65Zn to measure ultrafilterable zinc concentration revealed no change in ultrafilterable zinc during glucagon infusion. In a third series of experiments, acetylcholine (25 micrograms/min) was infused into one renal artery while zinc excretion and renal function of the two kidneys were compared. Acetylcholine did not significantly alter zinc excretion despite large changes in sodium and water excretion. The changes in zinc excretion observed in all experiments correlated well with glomerular filtration rate changes, but additional contributions of changes in tubular handling of zinc cannot be ruled out.
Electrical effects of acidification in the rabbit proximal convoluted tubule
Authors: Berry C. A.
Published: December 2017

The electrical characteristics of acidification were examined in isolated rabbit proximal convoluted tubules (PCT). In PCT perfused and bathed with an ultrafiltrate-like solution, the transepithelial potential difference due to active transport (transport PD) averaged -2.4 mV. The transport PD shifted in a negative direction by 1 mV (to -3.4 mV) when carbonic anhydrase inhibitors were added to the bath solution, and in a positive direction by 1.4 mV (to -1.0 mV) when bath sodium bicarbonate concentration was lowered. The positive shift was prevented by addition of either carbonic anhydrase inhibitors or the anion transport inhibitor SITS to the bath. These findings suggested electrogenic acidification. However, when electrogenic sodium transport was inhibited by removal of glucose and alanine from the luminal fluid, a positive PD suggesting electrogenic acidification was not observed. In tubules lacking glucose and alanine in the luminal fluid the rate of total CO2 absorption was 97.2 before and 35.4 pmol.mm-1.min-1 after inhibition of carbonic anhydrase. These findings do not support an independent electronic acidification mechanism. Nonelectrogenic acidification may secondarily after transepithelial PD by changes in transcellular current flow or by changes in paracellular resistance.
Urate transport by the isolated perfused S2 segment of the rabbit
Authors: Senekjian H. O. , Knight T. F. , Weinman E. J.
Published: December 2017

Urate transport was studied in isolated perfused S2 segments of the superficial proximal tubule of the rabbit. When urate was present in identical concentrations of 290 microM in the perfusing and bathing solutions, there was a net secretory flux of urate of 775.0 +/- 152.8 fmol.min-1.mm-1. When urate was present in varying concentrations in the bathing solution only, the bath-to-lumen flux of urate increased as the concentration of urate in the bathing solution was increased from 60 to 595 microM, but tended toward a plateau at higher concentrations. After correction of the net secretory flux for the contribution of passive permeation, an apparent Km of 238 microM and Vmax of 950 fmol.min-1.mm-1 for the secretory flux of urate was calculated. When urate was present only in the luminal perfusion solution, the lumen-to-bath flux of urate was significantly less than the bath-to-lumen flux at a similar bath concentration of urate. The lumen-to-bath flux of urate was not significantly affected by cooling the bath to 25 degrees C. These studies provide evidence for both passive and facilitated mechanisms for urate secretion in the rabbit S2 segment. The absorptive flux for urate, however, appears to be primarily a passive mechanism.
Effect of albumin on the function of perfused rat kidney
Authors: Schurek H. J. , Alt J. M.
Published: December 2017

The effect of different albumin concentrations on whole kidney function has been studied in the isolated perfused rat kidney. When a dialyzer was included in the perfusion circuit, GFR and sodium transport remained nearly constant for 2 h. Perfusion flow rate was directly correlated with albumin concentration. GFR was low (0.56 ml.min-1.g-1) at high albumin concentration (7.6 g/100 ml) and highest (1.38 ml.min-1.g-1) when albumin was omitted. The latter observation differed from earlier findings by other investigators who found a reduced GFR in the absence of albumin. This reduced GFR could be explained by ureteral backpressure, which results from the use of narrow ureter catheters. Fractional sodium reabsorption was approximately 50% irrespective of load when albumin was absent, and reached 90% at a GFR of 0.95 ml.min-1.g-1 when 5-6 g/100 ml albumin was used. At reduced load, fractional sodium reabsorption approached in vivo values of 98%. Potassium secretion was observed at high urinary flow rates when albumin concentration was low; low urinary flow rates at high protein concentration were associated with net potassium reabsorption.
Transmembrane electrical potential differences in cells of isolated renal tubules
Authors: Terreros D. A. , Tarr M. , Grantham J. J.
Published: December 2017

Isolated fragments of renal tubules were prepared by treating rabbit kidneys removed from animals on a normal diet with proteolytic enzymes. The intracellular potential of tubule cells was measured either by impaling cells across the luminal membrane at the everted end of the tubule or by impaling cells across the basolateral membrane along the shaft of the tubule. The mean intracellular potential recorded from 163 cells at the everted ends of proximal tubules was -49 +/- 12 mV (SD) compared with a mean value of -29 +/- 9 mV (SD) recorded from 199 cells along the shaft of the tubules. In papillary collecting ducts there was no significant difference between the intracellular potential of cells at the everted end of the tubules compared with those of cells along the shaft of the tubule. However, two distinctly different types of intracellular potentials were recorded from collecting duct cells regardless of the location of the cells: 93 cell impalements gave a mean intracellular potential of -15 +/- 8 mV (SD), whereas 135 cell impalements gave a mean potential of +24 +/- 12 mV (SD). The data presented in this paper demonstrate that intracellular potentials can be recorded from isolated renal tubule fragments of papillary collecting ducts and proximal convoluted tubules.
Indomethacin impairs water diuresis in the DI rat: role of prostaglandins independent of ADH
Authors: Stoff J. S. , Rosa R. M. , Silva P. , Epstein F. H.
Published: December 2017

The mechanisms by which endogenous renal prostaglandins regulate water excretion were investigated in these studies. Inhibition of prostaglandin synthesis slowed water diuresis in water-loaded unanesthetized Sprague-Dawley rats and in Brattleboro rats with hereditary diabetes insipidus owing to absence of endogenous vasopressin. In both strains, treatment with indomethacin or meclofenamate increased the osmolality of the renal papilla by raising sodium and urea content, and also increased the osmolality of the urine. Endogenous creatinine clearance and solute excretion were unchanged. The data are consistent with an effect of prostaglandins on solute transport by renal tubules and demonstrate that endogenous prostaglandins influence water excretion by a mechanism independent of the presence of antidiuretic hormone.
Spectrophotometric monitoring of O2 delivery to the exposed rat kidney
Authors: Balaban R. S. , Sylvia A. L.
Published: December 2017

Optical spectrophotometry was used to measure changes in the oxidation-reduction state of cytochrome c oxidase in the in situ rat kidney. Alterations in the redox state of cytochrome c oxidase were monitored during variations in the amount of oxygen being delivered to the animal. Spectral analyses were performed on whole kidney, cortical tubule suspensions, and blood (the latter flowing freely through surgically implanted femoral arteriovenous shunts). Reaction spectra identified the location of the absorption maxima for reduced cytochrome c oxidase to be at approx. 605 nm. Additional spectral analysis indicated that hemoglobin oxygenation-deoxygenation changes had minimal artifactual interference on the cytochrome redox signals. The present results indicate that mitochondrial cytochrome c oxidase is not maximally oxidized in the in situ kidney of anesthetized rats at arterial oxygen in the in situ kidney of anesthetized rats at arterial oxygen tensions within the normal physiological range. The redox state of the enzyme in vivo is altered by changes in the level of inspired oxygen over a wide range. The current data are consistent with the existence of nonuniform regions of aerobic respiration occurring in the in situ kidney.
Regulation of the PTH-receptor-cyclase system of canine kidney: effects of calcium, magnesium, and guanine nucleotides
Authors: Bellorin-Font E. , Martin K. J.
Published: December 2017

These studies examine the interactions of Ca2+, Mg2+, and guanine nucleotides with PTH binding to renal receptors and activation of adenylate cyclase in a purified preparation of basolateral renal cortical membranes. Inhibition of adenylate cyclase activity by increasing concentrations of CA2+ was more pronounced in the presence of PTH than on basal activity. This effect was not explained by an effect of Ca2+ on equilibrium PTH binding or binding affinity. The presence of PTH also decreased the requirements of the enzyme for Mg2+, consistent with the competitive nature of Ca2+ and Mg2+ interaction. Guanine nucleotides produced similar changes in the metal requirements for enzyme activity. PTH and guanine nucleotides, however, were not additive in this regard in spite of marked synergism in total enzyme activity. Additional studies were performed to further define the effects of guanine nucleotides on the receptor-cyclase system. GTP and Gpp(NH)p caused a dose-dependent decline in equilibrium PTH binding and a small increase in half-maximal displacement. PTH-stimulated adenylate cyclase activity was markedly increased by either nucleotide, and the half-maximal activity was decreased (Gpp(NH)p greater than GTP). This was partly explained by a marked effect of guanine nucleotides on the dissociation rate of receptor-bound PTH. These data suggest that Ca2+ inhibition of PTH-stimulated adenylate cyclase activity is not due to a decreased binding of PTH but to an effect of PTH on the metal requirements for adenylate cyclase activation at the nucleotide regulatory site.
NaCl transport in mouse medullary thick ascending limbs. II. ADH enhancement of transcellular NaCl cotransport; origin of transepithelial voltage
Authors: Hebert S. C. , Culpepper R. M. , Andreoli T. E.
Published: December 2017

We measured the relations between tubular perfusion rate and the rate of net NaCl transport in medullary thick ascending limbs of Henle (mTALH) either in the presence or absence of ADH. These data, together with the known Na+, Cl-, and water permeability characteristics of the mTALH, were used to calculate tau NaCl (mol . s-1 . cm-2), the rate of conservative Cl- transport from lumen through cells to interspaces; and CNaCl, the effective NaCl concentration in lateral intercellular spaces. The experimental results indicate that in these tubules the rate of net Cl- absorption increases monotonically with perfusion rate, and that at a given perfusion rate ADH increases the rate of net salt absorption. The theoretical calculations show clearly that the ADH-mediated increase in salt absorption depends on an increase in the rate of conservative transcellular Cl- transport. However, the present analytical data do not permit a distinction between wholly electroneutral apical membrane NaCl entry with respect to a process in which apical membrane Na+/Cl- entry has a stoichiometry less than unity, and electrogenic Na+ transport accounts for the remaining component of net Na+ absorption. Identification of the stoichiometry of the Na+/Cl- apical membrane entry step will depend, among other factors, on identifying explicitly the diffusion resistance of paracellular fluid and the mode of passive ion transport across junctional complexes.
Effect of norepinephrine and renal denervation on renal PGE2 and kallikrein in rats
Authors: Diz D. I. , Baer P. G. , Nasjletti A.
Published: December 2017

To investigate the influence of the sympathetic nervous system on the renal prostaglandin and kallikrein systems we studied the effects of norepinephrine (NE) infusion and renal denervation on the urinary excretion of prostaglandin E2 (PGE2) and kallikrein in unanesthetized rats. Relative to sham controls, in rats infused with NE at 15 micrograms/h i.p. for 8 days. plasma NE was increased 10-fold, systolic blood pressure by 20-34 mmHg, and urinary PGE2 excretion twofold, but urinary kallikrein excretion was not altered. Norepinephrine infusion also produced a transient natriuresis and a slight reduction in body weight gain. Relative to values in sham-operated rats, bilateral renal denervation reduced catecholamine content of the kidneys to less than 10% of control 10 and 30 days after surgery, but had no effect on urinary excretion of either PGE2 or kallikrein. It is concluded that in unanesthetized rats a) renal kallikrein is not affected by either a sustained increase in plasma norepinephrine or by chronic renal artery denervation, b) basal renal PGE2 production is not regulated by basal renal nerve activity, and c) prolonged elevation of plasma norepinephrine causes, either directly or indirectly, a sustained induction of PGE2 production by the kidney.
A subcutaneous capsule for long-term studies
Authors: Senay L. C. , Mitchell G. , McClain E. , Mitchell D. , Connors N.
Published: December 2017

In assessing interstitial fluid dynamics, perforated capsules have a limited existence because of the ingrowth of connective tissue. A permanently patent capsule (1 yr) can be obtained by implanting 1.9-cm lengths of Tygon tubing (OD 7.9 mm, ID 4.8 mm). After implant, the capsule is invested in connective tissue, and a thin strand of connective tissue invades both ends of the capsule. In 2–3 wk, the connective tissue joins in the capsule and there is no further ingrowth of connective tissue. This tissue bridge through the center of the capsule is richly vascularized, eventually containing small central arteries and veins. Protein content of capsule fluid was 50–60% of plasma, with albumin proportionately higher in the capsule. Intracapsule pressures averaged -2.08 mmHg. Communication between capsule contents and vascular volume appeared to be size-dependent in that the [35S]sulfate and [3H]inulin count could be measured in tail blood 5 min after intracapsule injection and it increased over 30 min. This did not occur with [14C]dextran (mol wt 70,000) and [14C]globulins (mol wt 150,000). This capsule appears to lend itself to long-term studies related to interstitial fluid dynamics and/or capillary exchange.
Functional adaptation to reduced renal mass in early development
Authors: Chevalier R. L.
Published: December 2017

To determine whether reduced renal mass in the newborn results in acceleration of normal renal development, the response to unilateral nephrectomy (N) before 36 h of age was compared with sham-operated (S) guinea pigs during the period of most rapid nephron maturation. Studies were performed at 7-13 days (group I) and 19-25 days (group II). Mean arterial blood pressure (AP), left kidney glomerular filtration rate (LKGFR), and urine sodium excretion (UNaV) were measured. Superficial single nephron GFR (sSNGFR) and proximal fractional water reabsorption (FRH2O) were measured by micropuncture, and the number of glomeruli (NG) was determined by India ink perfusion. In view of the susceptibility of the neonate to extracellular fluid loss, groups I and II were plasma infused to maintain euvolemia and group II was compared with 19- to 25-day-old hydropenic animals (group III). Increase in body weight with age was unaffected by neonatal N. In group IN, the compensatory increase in sSNGFR was greater than SNGFR for deeper nephrons, which normally contribute most to GFR at this age. In group IIN there was an 80% adaptive increase in LKGFR that could not be entirely explained by the rise in SNGFR. Since NG in group IIN was greater than in group IIS and similar to that in adulthood, the enhanced adaptation in LKGFR in group IIN may be due in part to earlier recruitment of a population of underperfused glomeruli. FRH2O did not change significantly with age and did not differ in N and S groups. Animals in group III developed a rise in hematocrit during the experiment, and AP, LKGFR, and UNaV were lower in group IIIN than in group IIN. It is concluded that following N at birth, the sequence of renal functional maturation is accelerated while glomerulotubular balance is preserved. As a result of these adaptative changes, homeostasis is maintained and body growth proceeds without impairment.
A proposed role for adenosine in the regulation of renal hemodynamics and renin release
Authors: Spielman W. S. , Thompson C. I.
Published: December 2017

Adenosine is produced by renal tissue and has potent effects on renal blood flow and its distribution, glomerular filtration rate (GFR), and the secretion of renin. Intrarenal infusion of adenosine decreases GFR primarily by decreasing glomerular hydrostatic pressure through its effects in increasing afferent arteriolar resistance and possibly decreasing efferent arteriolar resistance. The fall in GFR due to adenosine is accompanied by little change or an increase in total organ blood flow. Regional renal blood flow during adenosine infusion is redistributed, with a greater percentage of total flow going to the juxtamedullary cortex. Intrarenal adenosine produces marked decreases in water and sodium excretion that are proportionally greater than its effect on GFR, suggesting a possible direct tubular action. Intrarenal adenosine also produces a rapid and pronounced inhibition of renin release that appears to be independent of its hemodynamic or tubular effects. A metabolic hypothesis for the control of glomerular filtration rate and renin release with adenosine acting as a mediator is considered, and criteria for establishing an intrarenal role for adenosine in the regulation of renal function are discussed.
Transcapillary exchange of molecular weight markers in the postglomerular circulation: application of a barrier-limited model
Authors: Trainor C. , Silverman M.
Published: December 2017

The permselectivity of the postglomerular capillary wall was studied by performing pulse-injection multiple indicator-dilution experiments on dog kidneys in vivo, using simultaneous injection of T1824-labeled albumin (plasma reference), creatinine (extracellular reference), and one or two radioactively labeled indicators: raffinose (595 dalton), vitamin B12 (1,357 dalton), or inulin (approximately 5,000 dalton). The urine transit patterns superimposed for all these except albumin, suggesting equal permeability for these molecular weight markers at the level of the glomerular filtration barrier. But the renal vein mean transit times progressively decreased. Therefore, their apparent interstitial volumes of distribution decrease with increasing molecular weight. This could be due to several factors acting singly or in combination: reduced capillary permeability in the postglomerular microcirculation; restricted diffusion in the postglomerular interstitium; or excluded volume effects. Evidence suggested that the effect was due to a combination of permeability and exclusion volume effects. To assess the validity of this assumption, the barrier-limited model was compared with the experimental data. The results were analyzed (both hydropenic and mannitol-diuretic dogs) and best fits calculated using two independent parameters, permeability and excluded volume. For permeability (X10(-4) cm/s, mean +/- SD) the range of values was always greater than or equal to 15 for creatinine and raffinose, and greater than or equal to 12 for B12. The permeability for inulin was 6.9 +/- 1.4. When interstitial volume excluded was expressed as percentage of the volume available to creatine, the excluded volume was negligible for raffinose and B12 but 12 +/- 5% for inulin. During mannitol diuresis the permeability for creatinine and raffinose remained high, but the values tended to decrease for B12. The permeability of inulin decreased to 2.9 +/- 0.09. Mannitol diuresis increased the excluded volume of inulin but did not alter the creatinine, raffinose, or B12 value.
Nicotinamide restores phosphaturic effect of PTH and calcitonin in phosphate deprivation
Authors: Berndt T. J. , Pfeifer J. D. , Knox F. G. , Kempson S. A. , Dousa T. P.
Published: December 2017

Results of previous studies suggest a potentially important role for nicotinamide adenine dinucleotide (NAD) in the cellular regulation of phosphate transport by the renal proximal tubules. The present clearance studies were performed to evaluate whether intraperitoneal administration of nicotinamide, a precursor of NAD and inhibitor of NAD catabolism, would not only increase phosphate excretion but also restore the phosphaturic response to parathyroid hormone (PTH) in rats fed a low phosphate diet. Rats fed a low phosphate diet were resistant to the phosphaturic effect of PTH, calcitonin, and dibutyryl cAMP (DBcAMP) in spite of the fact that all three agents elicited an increase in the urinary excretion of cAMP. Administration of nicotinamide to rats fed a low phosphate diet increased renal cortical NAD levels, increased phosphate excretion, partially restored the phosphaturic effect of PTH and DBcAMP, and completely restored the phosphaturic response to calcitonin. We conclude that nicotinamide restores the phosphaturic effect of PTH and calcitonin in rats fed a low phosphate diet by acting at a cellular step subsequent to cAMP generation to inhibit tubular reabsorption of phosphate.
Control mechanisms of bicarbonate transport across the rat proximal convoluted tubule
Authors: Chan Y. L. , Biagi B. , Giebisch G.
Published: December 2017

Bicarbonate transport (JHCO3) was studied in rat proximal convoluted tubules by luminal and peritubular microperfusion, and the effects on tubular bicarbonate transport of selective changes in luminal and peritubular bicarbonate concentrations and of changes in luminal flow rate were evaluated. A pH glass electrode was used to measure [HCO3(-)] and gave results similar to those of a microcalorimetric method. Increasing the tubular and peritubular [HCO3(-)] at constant luminal perfusion rate (10 nl.min-1) augmented JHCO3, but JHCO3 increased more when pH changes were prevented by PCO2 adjustments (constant peritubular pH) than when pH was allowed to rise with the increase in [HCO3(-)] (constant PCO2). Elevation of the tubular HCO3(-) load by raising [HCO3(-)] stimulated JHCO3 more than when the HCO3(-) load was raised by enhancing luminal perfusion rate at constant [HCO3(-)] An increase in PCO2 at constant peritubular pH increased JHCO3. Diamox and benzolamide inhibited JHCO3 at luminal concentrations of 2-4 X 10(-4) M, yet a small but significant fraction of JHCO3 remained intact. Capillary perfusion with 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (5 X 10(-4) M) depressed JHCO3 by 70%. Acute changes in luminal and peritubular potassium concentrations (range, 2-6 meq/liter) had no effect on JHCO3, but JHCO3 increased moderately but significantly in severe dietary hypokalemia.
Atrial receptor modulation of renal nerve activity in the nonhuman primate
Authors: Gilmore J. P. , Echtenkamp S. , Wesley C. R. , Zucker I. H.
Published: December 2017

Experiments were done in the nonhuman primate Macaca fascicularis to determine the extent to which low-pressure receptors modulate renal nerve activity (RNA). Left atrial pressure (LAP) was increased either by inflating a balloon in the left atrium or by intravascular volume expansion. Arterial pressure (AP) was increased by the administration of epinephrine. Balloon inflation produced variable changes in RNA when all reflexes were intact. In the bilateral vagotomized animal, balloon inflation significantly increased RNA. Compared with the intact state, neither carotid sinus denervation nor sinoaortic denervation had a significant influence on RNA during balloon inflation. The response of both baroreceptor-denervated groups, however, was significantly less than that of the vagotomized group. Vagotomy plus sinoaortic denervation essentially prevented any effect of balloon inflation on RNA. Volume expansion produced a greater inhibition of RNA per increase in AP than did epinephrine. However, this difference was abolished after bilateral cervical vagotomy. These experiments demonstrate a significant influence and interplay of low- and high-pressure receptors on RNA in the nonhuman primate.