bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of lactate infusion on myocardial FFA metabolism in diabetic dogs
Authors: Spitzer JJ
Published: December 2017

The effect of elevated arterial lactate concentration on myocardial free fatty acid (FAA), acetoacetate (AcAc), and beta-hydroxybutyrate (beta-OHB) uptake was studied in alloxan-diabetic dogs under control conditions and following the constant infusion of Na-L-(+)-lactate. Only minor changes in hemodynamic parameters were observed. During lactate infusion, arterial lactate increased and FFA, AcAc, and beta-OHB decreased. The extraction ratio and myocardial uptake of both AcAc and beta-OHB diminished. No significant change of myocardial FFA oxidation was noted. While myocardial lactate uptake was very small under control conditions, it increased considerably during the infusion of lactate. The fraction of myocardial CO2 production derived from FFA oxidation was unchanged during lactate infusion, while the fraction derived from ketone bodies decreased and that derived from lactate increased. Thus, during hyperlactacidemia a larger fraction of myocardial substrate was derived from lactate and a smaller fraction from ketone bodies than were derived under control conditions.
Ionic requirements of proximal tubular sodium transport. I. Bicarbonate and chloride
Authors: Green R , Giebisch G
Published: December 2017

Simultaneous perfusion of peritubular capillaries and proximal convoluted tubules was used to study the effect of varying transepithelial ionic gradients on ionic fluxes. Results show that net sodium influx and volume flux was one-third of normal when bicarbonate was absent, no chloride gradient existed, and glucose and amino acids were absent. Addition of bicarbonate to the luminal fluid did not restore the flux to normal, but peritubular bicarbonate did restore it. A chloride gradient imposed when no bicarbonate was present could only increase the fluxes slightly, but his flux was significant even after cyanide had poisoned transport. Reversing the chloride concentration gradient decreased the net sodium and volume fluxes whether bicarbonate was present or not. Glucose had no effect on fluxes, but substitution of Na by choline abolished them entirely. It is concluded that sodium is actively transported, that a chloride concentration gradient from lumen to plasma could account for up to 20% of net transport, and that peritubular bicarbonate is necessary for normal rates of sodium and fluid absorption.
Intracellular pH and K+ of cardiac and skeletal muscle in acidosis and alkalosis
Authors: Poole-Wilson PA , Cameron IR
Published: December 2017

The effects of a metabolic and respiratory acidosis and alkalosis on intracellular pH (pHi) and K+ have been compared in cardiac and skeletal muscle from the anesthetized rabbit. The extracellular space and pHi were calculated from the distribution volumes of [51Cr] EDTA and [14C]DMO, respectively. When pHe was varied by altering PCO2, the slope of the line relating pHi to the extracellular pH (pHe) was greater (P less than 0.05--0.001) than that obtained during metabolic changes of pHe in right and left ventricles, atria, diaphragm, and quadriceps. During metabolic acidosis and alkalosis, the slope of pHi/pHe line did not vary between tissues. During respiratory acidosis, there was no difference in slope between cardiac tissues, but it was less in left ventricle than quadriceps (P less than 0.001). In left ventricle intracellular K+ increased in a metabolic (P less than 0.05) or respiratory acidosis (P less than 0.02), whereas in diaphragm it decreased (P less than 0.02). Intracellular K+ correlated with pHe and pHE-PHi. Changes in pHi but not intracellular K+ could explain known differences in myocardial function in respiratory and metabolic acidosis.
Effect of ethanol on phospholipid metabolism by the rat lung
Authors: Wagner M , Heinemann HO
Published: December 2017

Prefeeding of alcohol shows the in vivo incorporation of orally administered palmitic acid into phosphatidylcholine of the lung. This impairment is also demonstrable in vitro utilizing lung slices and 14C-labeled palmitate or cytidine 5'-diphosphocholine as precursors. It is concluded that alcohol ingestion affects the utilization of precursors needed for phospholipid formation in the lung.
3H2O volume and exchange in uterine cavity of monkeys
Authors: Shaw ST  , Azar E , Moyer DL
Published: December 2017

A technique was developed to measure water exchange in the endometrical canal (uterine cavity). This type of determination should provide information necessary to understanding intrauterine pharmacokinetics. In the study described, measurements were performed on one cynomologus and four rhesus monkeys. Endometrial fluid in the uterine cavity was replaced with a 3H2O solution of known specific radioactivity (dpm/ml). Radioactivity remaining in the cavity at measured intervals of approximately 0.5, 1, 2, and 3 min following replacement was determined by flushing out the cavity. By extrapolating the 3H2O disappearance curve versus time to t = 0 (zero time), the apparent cavity volume (aVc) was derived. Values for aVc and t 1/2 3H2O were used to calculate endometrial fluid-water turnover rate. Mean values determined in four rhesus monkeys were as follows: aVc, 0.032 ml; t 1/2 H2O, 1.17 min; 24-h H2O turnover, 19.5 ml. In general, this value for H2O turnover was considerably higher than values of endometrial fluid production quantitated by other techniques. Water measurements in human uteri similar to those reported here appear feasible and are anticipated in future work.
Regulation of protein kinase by vasopressin in renal medulla in situ
Authors: Dousa T. P. , Barnes L. D.
Published: December 2017

Results of this study demonstrate that vasopressin activates protein kinase in intact renal medullary cells as detected by measurement of the (-cyclic AMP/+cyclic AMP) protein kinase activity ratios in freshly prepared tissue extracts (40,000 X g supernates) from bovine renal medullary slices. The activation of protein kinase was specific for vasopressin since parathyroid hormone, histamine, angiotensin II, or the inactive analog of vasopressin did not activate protein kinase. There was a direct correlation between the extent of protein kinase activation and the elevation in tissue levels of cyclic AMP elicited by increasing doses of vasopressin or with an increase in incubation time. The elevation of tissue cyclic AMP level and maximum activation of protein kinase reached maximum level at a vasopressin concentration of about 2 X 10(-9) M. Incubation of slices with vasopressin caused a dose-dependent decrease in the cyclic AMP-dependent protein kinase activity in the 40,000 X g supernate of homogenate from the renal medullary slices. This effect of vasopressin was specific for protein kinase since activity of lactate dehydrogenase or a specific [3H]colchicine-binding activity was not affected, and the decrease in the protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase activity extracted from 40,000 X g pellets of homogenate prepared from slices exposed to vasopressin. Results thus provide evidence that cyclic AMP-mediated protein kinase activation in the intact cells is an integral part of cellular response of the mammalian renal medulla to vasopressin.
Renal electrolyte circadian rhythms: independence from feeding and activity patterns
Authors: Moore-Ede M. C. , Herd J. A.
Published: December 2017

The interrelationships between urinary electrolyte circadian rhythms and rhythms of feeding, drinking and activity were studied in six conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) kept in temperature-controlled isolation chambers on a light-dark (LD) 12:12 h cycle. With lights on (600 lx) from 0800 to 2000 h and off (less than 1 lx) from 2000 to 0800 h, renal potassium excretion in monkeys fed ad libitum fell to a daily minimum of 64 +/- 6 mueq/h at 0500 h and rose to a maximum of 274 +/- 13 mueq/h at 1700 h. Sodium excretion fell to a minimum of 13 +/- 2 mueq/h at 1000 h and rose to a maximum of 43 +/- 6 mueq/h at 2100 h, while water excretion fell to a minimum of 869 +/- 63 mul/h at 0500 h and rose to a maximum of 2,307 +/- 222 mul/h at 1700 h. Feeding, drinking, and activity occurred only during the lights-on period. Independence of the urinary rhythms from diurnal variations in feeding, drinking, and activity was established a) by depriving monkeys of food, b) by depriving monkeys of water, and c) by training monkeys to perform a 2-hourly schedule of feeding, drinking, and activity throughout day and night. None of these three regimens resulted in major reductions of the amplitude, or changes in the phase of the circadian rhythms of urinary electrolyte or water excretion. These findings indicate that the circadian rhythms of urinary potassium, sodium, and water excretion are controlled by mechanisms that are not passively dependent on the behavioral patterns of feeding, drinking, and activity.
Potassium activity and plasma membrane potentials in epithelial cells of toad bladder
Authors: Kimura G. , Urakabe S. , Yuasa S. , Miki S. , Takamitsu Y.
Published: December 2017

Intracellular potassium activity (aki), mucosal and serosal membrane potential (mEm, sEm), short-circuit current (Isc), and transepithelial potential difference in the epithelium of the toad bladder were measured with a potassium-sensitive liquid ion exchanger and an ordinary microelectrode. Under basal conditions, aki was 41.2 +/- 0.5 mM, corresponding to 54.4 mM in free potassium concentration, so half or more of the intracellular potassium may be of bound form or sequestrated within subcellular organelles. The sEm cannot be explained by only the potassium equilibrium potential (Eeq), because the sEm was markedly lower than the Eeq and no relation was found between them. Ouabain and rotenone decreased the aki, but ethacrynic acid, which also inhibited the Isc and the membrane potentials, did not show any effect on aki. Vasopressin decreased aki with an elevation in mEm, whereas prostaglandin E1 increased the aki with elevation in the sEm. These characteristic changes may afford an insight into the mechanisms by which transcellular electrolyte transport occurs.
Insulin-mediated Na+ transport in the toad urinary bladder
Authors: Cox M. , Singer I.
Published: December 2017

The characteristics of insulin-induced Na+ transport in the toad urinary bladder were determined and compared to those of aldosterone. Bladders were mounted in modified Ussing chambers, and standard short-circuit current techniques were employed to measure transepithelial Na+ transport. Insulin added to the serosal medium is much more effective than insulin added to the mucosal medium. Serosal insulin concentrations from 10(1) to 10(3) muU/ml increase both the initial rate and the final level of Na+ transport achieved, whereas concentrations from 10(3) to 10(5) muU/ml increase only the initial rate of Na+ transport. Insulin-induced Na+ transport probably does not require glucose. Both insulin- and aldosterone-induced Na+ transport are directly proportional to serosal (but not mucosal) K+ concentration over the physiologic range (2.0-7.0 meq/liter). However, cycloheximide abolishes aldosterone- but not insulin-induced Na+ transport. In addition, insulin stimulates Na+ transport after a maximal response to aldosterone, and aldosterone stimulates Na+ transport after a maximal response to insulin. Thus, although they have several similar characteristics, insulin and aldosterone have at least partially independent mechanisms of action on Na+ transport in the toad urinary bladder.
Nephron filtration rate in conscious rats recovering from anesthesia
Authors: Bonvalet J. P. , Champion M. , Wanstok F. , Berjal G.
Published: December 2017

Single-nephron glomerular filtration rate (SNGFR) of superficial (S) and juxtamedullary (JM) nephrons was measured in conscious rats with a [14C]ferrocyanide infusion technique. Experiments were carried out in nondiuretic (ND), salt-loaded (SL), and hemorrhagic hypotensive (HH) rats. Mean SNGFR values of S and JM nephrons were 48.7 +/- 4.5 SE and 61.7 +/- 4.2 in ND, 73.6 +/- 8.7 and 87.5 +/- 10.8 in SL, and 29.9 +/- 5.9 and 36.4 +/- 7.1 in HH rats. These values are higher than the values reported in anesthetized rats. The S-to-JM SNGFR ratio was not significantly different in the three experimental conditions (ND, 0.788 +/- 0.032; SL, 0.843 +/- 0.018; and HH, 0.824 +/- 0.030), and did not differ from the values reported in anesthetized rats in similar experimental conditions. It is concluded that anesthesia exerts a depressive effect on GFR, but does not modify intrarenal SNGFR distribution. Neither saline loading nor hemorrhagic hypotension induces SNGFR intrarenal redistribution in conscious rats.
Effect of sodium fluoride on concentrating and diluting ability in the rat
Authors: Wallin J. D. , Kaplan R. A.
Published: December 2017

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.
Renal response to vasopressin after inhibition of prostaglandin synthesis
Authors: Fejes-Toth G. , Magyar A. , Walter J.
Published: December 2017

The renal effects of vasopressin (VP) in water-loaded and hydropenic conscious dogs were examined with and without the previous administration of prostaglandin (PG) synthesis inhibitors (indomethacin and meclophenamate). The parameters studied were: urinary output, sodium and potassium excretion, plasma and urinary osmotic concentration, total renal blood flow, mean arterial pressure, heart rate, and the clearance and extraction ratio of p-aminohippuric acid and inulin. The infusion of VP caused antidiuresis and marked saluresis during water diuresis, whereas it was found to be diuretic and saluretic in hydropenic animals. Inhibition of PG synthesis greatly enhanced the antidiuretic activity of VP and abolished its saluretic and diuretic actions. Changes in renal water and solute excretion and changes in the hemodynamic parameters are uncorrelated. It is concluded that intrarenal PGs may play an important role in modulating the renal action of VP.
Renal lymph protein in the rat
Authors: Hargens A. R. , Tucker B. J. , Blantz R. C.
Published: December 2017

Renal lymph and systemic (posterior) lymph were studied in hydropenic rats. As a consequence of the anatomical arrangement of collecting lymphatics near the kidney, mixed renal and systemic lymph tributaries are situated in such a way that sampling pure renal lymph is difficult. Pure renal lymph contains 1.0 +/- 0.1 g/100 ml total protein with an albumin-to-globulin (A/G) ratio of 2.1 +/- 0.1. Mixed renal and extrarenal lymphatic tributaries contain 3.3 +/- 0.2 g/100 ml total protein with an A/G ratio of 1.8 +/- 0.2. Corresponding values in the plasma are 4.9 +/- 0.2 and 1.2 +/- 0.1 g/100 ml, respectively. Previous studies in which the concentration of renal lymph protein was determined as 30-50% of that in plasma were probably in error due to contamination of renal samples by posterior lymph ducts. The amount of systemic and renal lymph mixing is highly variable from one animal to another. Our renal lymph samples in carefully controlled and prepared Munich-Wistar rats contained a total protein uniformly 20% of that in plasma.
Ion pumps in the renal tubule
Authors: Sachs G.
Published: December 2017

Biochemical studies of renal tissue have so far not shown the presence of any active pump mechanism other than Na-K-ATPase. In this review of possible transport mechanisms for the ions Na, K, H, Cl, and HCO3, it is suggested that transport of these ions can be coupled to ATPase by conductance (uniport) processes or by ion gradients by co-transport (symport) or countertransport (antiport) systems. These may be neutral or electrogenic. Accordingly, the function of any region of the tubule will be determined by the porter(s) present in the apical or basal-lateral membrane, and by the Na-K-ATPase located almost exclusively in the basal-lateral membrane. Future research in this area will probably define these porters in vesicles isolated from specific cell types of the kidney.
Transport characteristics of renal collecting tubules: influences of DOCA and diet
Authors: O'Neil R. G. , Helman S. I.
Published: December 2017

Isolated renal cortical collecting tubules from rabbits were studied at random (control) and from rabbits maintained on diets containing either high or low Na and K content or injected with DOCA for up to 31 days. In general, the values of transepithelial voltage (VT) and electrical resistance (RT) varied considerably between tubules. When rabbits were fed a high K, low Na diet or were injected with DOCA the values of VT increased. Of interest was the observation that tubules obtained from rabbits maintained on DOCA for 11–18 days or longer possessed markedly elevated values of VT (mean VT, -54 mV) and a marked increase in their ability to reabsorb Na and secrete K at rates well above the levels observed even at 3–6 days of treatment when it was expected that maximal transport rates would have been achieved. From the estimates of the conductances of Na, K, and Cl, the data could be interpreted to mean that DOCA caused a decrease in the conductance of Cl, perhaps via the shunt pathway, while elevating the conductances of Na and K, thereby enhancing active Na and especially K transport by this nephron segment.
Effects of sodium and potassium salts with anions other than chloride on renin secretion in the dog
Authors: Stephens G. A. , Davis J. O. , Freeman R. H. , Watkins B. E.
Published: December 2017

Intrarenal arterial infusions of sodium and potassium salts with anions other than chloride were given to evaluate the role of the chloride ion in influencing renin secretion (RS). The studies were conducted in dogs with thoracic caval constriction. Sodium lactate increased renal venous plasma sodium concentration (RVPNa) from 142 to 166 meq/liter (n, 6); RS decreased from 3,070 to 1,510 ng angiotensin/min (P less than 0.005). Arterial blood pressure and renal blood flow were not changed appreciably. Sodium excretion (ENa) increased, whereas chloride excretion (EC1) fell during the first three 15-min infusion periods. Potassium lactate increased renal venous plasma potassium concentration from 4.1 to 6.2 meq/liter (N, b). RS decreased during the first three 15-min periods of infusion (from 3,470 to 2,180 ng angiotensin/min, P less than 0.01). ENa and EC1 increased during the infusion. Potassium sulfate also decreased RS, and EC1 was usually increased. The results with sodium lactate favor a role for sodium compared with chloride in mediating the decreased renin release, but there are other possible interpretations which have been discussed. Additional studies are needed to resolve the role of chloride during potassium infusion.
Renal and adrenal responses to [des-Asp1]angiotensin I in the dog
Authors: Freeman R. H. , Davis J. O. , Khosla M. C.
Published: December 2017

There is evidence for the endogenous generation of [des-Asp1]angiotensin II (AIII) from a nonapeptide precursor, [des-Asp1]angiotensin I ([des-Asp1]AI). In the present study, the effects of equipressor doses of exogeneously administered [des-Asp1]AI and AIII on renal function and plasma aldosterone concentration were compared. Intravenous infusion of [des-Asp1]AI (75 ng/kg min-1 for 40 min) decreased renin secretion, renal blood flow, creatinine clearance, and sodium and potassium excretion in dogs. Infusion of AIII at one-third of the rate of [des-Asp1]AI (25 ng/kg min-1) produced comparable decreases in these same parameters. Filtration fraction was increased with both peptides. Both peptides also increased plasma aldosterone concentration to the same extent. A bolus injection (5 mg i.v.) of the converting enzyme inhibitor SQ 20,881 completely reversed the mean arterial pressure and renal blood flow responses to [des-Asp1]AI, but did not alter these responses to AIII. These data are consistent with the concept that endogenous generation of AIII from [des-Asp1]AI can occur via the action of converting enzyme on this substance.
Bicarbonate absorption by rabbit cortical collecting tubules in vitro
Authors: McKinney T. D. , Burg M. B.
Published: December 2017

The rate of transport of bicarbonate was studied in isolated perfused rabbit cortical collecting tubules that were absorbing bicarbonate in vitro. Acetazolamide completely inhibited bicarbonate absorption, as was previously observed with isolated proximal tubules. Therefore, carbonic anhydrase probably is important for bicarbonate absorption in both the proximal tubules and collecting tubules. Inhibition of sodium transport by ouabain or elimination of its transport by completely removing the sodium did not cause a decrease in bicarbonate absorption by the collecting tubules. We previously found that inhibition of sodium transport caused a great decrease in bicarbonate absorption by proximal tubules. Therefore, absorption of bicarbonate is not directly related to sodium transport in collecting tubules, but it probably is related to sodium transport in isolated perfused rabbit proximal tubules. Amiloride inhibited bicarbonate absorption by the collecting tubules consistent with previous observations that the drug inhibits urinary acidification. Although amiloride also inhibits sodium transport and reduces the transepithelial voltage across the collecting tubules, the effect of the drug on bicarbonate transport apparently is independent of the other effects.
Transport in isolated plasma membranes
Authors: Hopfer U.
Published: December 2017

Plasma membrane vesicles constitute a simpler experimental system for studying transport compared to cells or intact tissue. The principal advantages of the vesicle approach are the elimination of metabolism as a complicating factor and the ability to control the composition of the solutions on both sides of the membrane. The major disadvantage is vesicle heterogeneity. However, techniques are available to avoid the kinetic artifacts that are due to the heterogeneity. Results of transport studies using membrane vesicles have conclusively shown that D-glucose and amino acids are co-transported with Na+ and that transport against a concentration gradient is driven by an electrochemical Na+ gradient. As a result of coupling between Na+ and the nonelectrolytes, estimates of the kinetic parameters of transport, Km and Vmax, require that the load on the Na+ gradient be taken into account. This has rarely been done. Although electrolyte transport is a major function of the plasma membrane, knowledge of the mechanisms involved is limited. Future investigations employing specific ionophores should contribute much to our understanding of the mechanisms underlying ATP-independent ion transport. Examples of the application of membrane vesicles for studying transport-related aspects of diseases are discussed.
Acetazolamide and renal ammoniagenesis
Authors: Chapman S. K. , Hoover M. S.
Published: December 2017

The effect of acetazolamide on ammonia-producing enzyme systems was determined in vitro at concentrations comparable to those which have been shown to abolish ammonium excretion in vivo. No change in the activity of glutaminase or gamma-glutamyl transpeptidase could be observed at concentrations up to 0.2 mM acetazolamide, and concentrations up to 1 mM were without effect on D-glutamyltransferase activity. Therefore, the effect of acetazolamide to abolish ammonium excretion cannot be explained by an action of the drug to inhibit ammoniagenesis.
Purification of distinct plasma membranes from canine renal medulla
Authors: Iyengar R. , Mailman D. S. , Sachs G.
Published: December 2017

Two types of plasma membrane were purified from canine distal renal medulla by the techniques of differential and zonal density-gradient centrifugation followed by free-flow electrophoresis. One group of plasma membranes was identified as basal-laterally derived based on a 30-fold enrichment of Na-K-ATPase, a 20-fold enrichment of vasopressin-stimulated adenylate cyclase, and a 33-fold enrichment of [3H]vasopressin binding sites. The second type of plasma membrane was free of these markers, but had a cholesterol and phospholipid composition similar to them. Alkaline phosphatase also had a similar distribution in the two fractions. This lighter membrane fraction contained a membrane-bound cyclic AMP-dependent protein kinase as well as substrate for this kinase. In addition there was a 26-fold enrichment of specific activity of an anion (SO32-)-activated ATPase which was insensitive to mitochondrial ATPase inhibitor protein, in contrast to the mitochondrial fraction of the tissue. Based on the relative preponderance of collecting duct tissue in the distal medulla and the yield of membrane protein, these membranes are tentatively identified as containing apical membranes of the collecting duct.
Comparison using central core model of renal medulla of the rabbit and rat
Authors: Foster D. M. , Jacquez J. A.
Published: December 2017

The studies presented here use a central core model of the renal medulla, the details of which have been given elsewhere (Foster et al., Mathematical Biosci. 32: 307–335, 337–360, 1976). The central core model of the rabbit medulla predicts concentration gradients and volume flow rates in line with what is known for the rabbit. The handling of urea, however, is not consistent with the scheme proposed by Kokko and Rector (Kidney Intern. 2: 214–233, 1972). Moreover, the low concentration of urea predicted for the urine suggests an absence in the model of some form of mediated transport for urea in the inner medulla. The central core model of the rat medulla failed to predict results consistent with what is known about the rat. Substitution of the rabbit thermodynamic parameters into the model for the rat resulted in predictions that more closely resembled what one might expect, but were not entirely satisfactory. The implication is that there may be an interspecies difference in the concentration machinery between the rabbit and rat.
Contribution of leaked load to solute transport by renal tubules
Authors: Warnock D. G. , Patlak C. S. , Burg M. B.
Published: December 2017

Renal tubules reabsorb solutes from the glomerular filtrate. The relationship between "filtered load" and reabsorption has been previously discussed and analyzed in detail. One aspect which has not been emphasized, however, is that, when reabsorption of a solute causes its concentration (or activity) in the tubule lumen to decrease below the level in the blood, solute may enter the tubule down this concentration gradient adding a "leaked load" to the filtered load. The leaked load should be taken into account when quantifying tubular transport. In the present study we derived equations for estimating the leaked load and its contribution to transport. The importance of the leaked load of glucose in the rabbit proximal convoluted tubules is evaluated with parameters derived from in vitro perfusion and by solving the equations numerically. It is shown that, depending on the conditions, the leaked load of glucose may account for a substantial part of the glucose present in the tubule lumen and reabsorbed from the tubule. Also, the leaked load could conceivably be an important factor in the transport of other solutes such as lactase and bicarbonate in proximal tubules.
Action of phlorizin on luminal and antiluminal membranes of proximal cells of kidney
Authors: Horsburgh T. , Cannon J. K. , Pitts R. F.
Published: December 2017

In accord with results of others, we have observed that the infusion of phlorizin at low rates (2.16-117 microgram-kg-1-min-1) progressively increases fractional excretion of glucose from 0.47 to 0.85. Further increasing the rate of infusion to 2.19 mg-kg-1-min-1 increases fractional excretion to 1.0. The relationship appears to describe a single function having characteristics of an adsorption isotherm. The metabolism of the kidney, expressed as rate of total CO2 production from all substrates, is modestly and variably reduced by infusion of phlorizin at both high and low rates. The metabolism of glucose, expressed as rate of CO2 production, is variably but not consistently altered by infusion of phlorizin. The oxidation of [14C]lactate derived from [14C]glucose is negligible and introduces no significant error into measurement of 14CO2 from [14C]glucose. The percent of total CO2 derived from glucose does not differe significantly in control periods from the mean of all periods following phlorizin. Accordingly interaction of phlorizin with peritubular membranes at high rates of infusion, in the sense of blocking penetration of glucose, does not occur. Our methods do not rule out nor do they prove adsorption of phlorizin to these membranes.
Urinary zinc excretion following infusions of zinc sulfate, cysteine, histidine, or glycine
Authors: Yunice A. A. , King R. W. , Kraikitpanitch S. , Haygood C. C. , Lindeman R. D.
Published: December 2017

Zinc sulfate (40 mg elemental zinc) or one of three amino acids (5 or 10 g cysteine, 10 g histidine, or 10 g glycine) was infused into anesthetized dogs over a 60-min period. Plasma concentrations and urine excretions of zinc and five other cations, and glomerular filtration rates were determined before, during, and after these infusions. Infusions of zinc sufficient to produce a 20-fold increase in total plasma zinc concentrations had little effect on urinary zinc excretions (threefold increase) or plasma ultrafilterable zinc concentrations. Ten grams of cysteine urinary zinc excretions more than 100-fold, 5 g of cysteine increased zinc excretions more than 30-fold, 10 g of histidine increased zinc excretions sixfold, and 10 g of glycine had no effect. Cysteine infusions appeared to produce a net tubular secretion of zinc. Only histidine appeared to increase serum ultrafilterable zinc concentrations significantly. It would appear that plasma and urine concentrations of certain amino acids, specifically cysteine and histidine, along with polypeptides and other metabolites containing these amino acids, may be major determinants of urinary zinc excretion.
Effects of renal fuels on uptake of PAH and uric acid by separated renal tubules of the rabbit
Authors: Kippen I. , Klinenberg J. R.
Published: December 2017

A rapid-filtration procedure was used to examine the effects of a wide variety of renal fuels on the uptake of p-aminohippuric acid (PAH) and uric acid (UA) by separated rabbit renal tubules. PAH and UA uptakes in 15 min over a range of substrate concentrations of 0.01-10.2 mM were determined. All tricarboxylic acid cycle intermediates and pyruvate showed biphasic stimulation of PAH and UA uptake. alpha-Ketoglutarate produced a 320 +/- 54% increase in PAH uptake and a 192 +/- 60% increase in UA uptake at 0.16 mM, the concentration at which uptake was maximal, while causing 20 +/- 3 (PAH) and 35 +/- 7% (UA) inhibition at 10.2 mM. Citrate produced a 373 +/- 19% increase in PAH uptake and a 246 +/- 41% increase in UA uptake at 0.64 mM. PAH and UA uptake were also stimulated by acetate, glucose frutose, phosphoenolypyruvate and L-glutamic acid. The data indicate a direct relationship between stimulation of PAH and uric acid transport and stimulation of renal cortical oxidative metabolism.
Further studies on ion permeation in proximal tubule of necturus kidney
Authors: Edelman A. , Anagnostopoulos T.
Published: December 2017

In the perfused Necturus kidney, the ratio of transepithelial sodium-to-chloride permeabilities (PNa/PCl) was estimated from dilution potentials at 1:7. The ratio of transepithelial permeabilities PHCO3/cl was estimated from bi-ionic potentials at 1:4 and that of Plact/PCl at 1:12. The permeability sequence, therefore, is PCl greater than PHCO3 greater than than PNa or PnaCl greater than PNaHCO3. The latter is similar to the situation in the rat. However, because of the low Na permeability, passive NaCl absorption by solvent drag is probably less important in Necturus than in the rat. The measurement of transepithelial input conductance during replacement of extracellular chloride by either bicarbonate or lactate shows that the former reduces the transmural conductance to 31% of control values as compared with 40% for the latter. Such discrepancies between permeability and conductance sequences are consistent either with an interference of the test anion with chloride permeation or with the presence of positive fixed changes within the shunt pathway.
Concentrative PAH transport by rabbit kidney slices in the absence of metabolic energy
Authors: Podevin R. A. , Boumendil-Podevin E. F. , Priol C.
Published: December 2017

Characteristics of para-aminohippurate (PAH) transport in the absence of intracellular metabolism were studied with Na+, K+-depleted and ouabain-poisoned rabbit kidney cortex slices. The imposition of a NaCl gradient (out to in) resulted in specific stimulation of PAH uptake. PAH accumulated against its concentration gradient when cell [Na+] was less than medium [Na+]. Conversely, renal cells extruded PAH when cell [Na+] exceeded medium [Na+]. Membrane potential measured with triphenylmethylphosphonium revealed that conditions which created an interior-positive membrane potential inhibited the Na+-dependent transport of PAH but caused stimulation of the Na+-independent component. Characteristics of the Na+-dependent PAH transport system in ouabain-poisoned slices were similar to those previously described in metabolically active tissues.
Iodide and thiocyanate efflux from brain following injection into rat caudate nucleus
Authors: Cserr H. F. , Berman B. J.
Published: December 2017

Mechanisms and pathways of 125I and 35SCN efflux from the brain were investigated in anesthetized rats. Tracers were injected into the caudate nucleus through a guide cannula implanted 1 wk previously and concentrations of isotope in brain and cerebrospinal fluid (CSF) were determined at various times after injection. 125I clearance from the brain followed a single exponential curve. In control rats 36.2% of the 125I remained in the brain 30 min after injection and 60.4% in rats pretreated with perchlorate. Comparable values for 35SCN were 25.8% in control rats, 41.0% with perchlorate, and 39.7% with iodide loading. Estimates of 125I and 35SCN effluxes from the brain via the blood-brain barrier and CSF pathways suggest that greater than 95% of efflux crosses the blood-brain barrier. These results indicate that 1)iodide and thiocyanate are transported across the blood-brain barrier by a common mechanism, and 2) this efflux system is an important factor in the control of the distributions of iodide and thiocyanate in the central nervous system.
Effect of ionophore RO 2-2985 on the efflux of calcium from the rat nephron
Authors: Senekjian H. O. , Knight T. F. , Ince A. , Weinman E. J.
Published: December 2017

The effect of the ionophore RO 2-2985 on the efflux of calcium from the renal tubule was studied employing the in vivo microinjection technique. Microinjection solutions contained either RO 2-2985 (E) or its diluent (C). Following microinjections into the early proximal tubule, urinary 45Ca recoveries averaged 10.1 +/- 1.9 (C) and 3.5 +/- 1.4% (E) (P is less than 0.005), while recoveries averaged 32.3 +/- 6.9 (C) and 24.9 +/- 6.5% (E) (P is less than 0.05) following microinjections into the late proximal tubule. To determine if the decreased recovery of calcium was a specific effect, the effect of RO 2-2985 on the efflux of sodium, phosphate, and 3-O-methyl-D-glucose was examined. Compared to controls, RO2-2985 did not affect the urinary recoveries of 22Na, [32P]orthophosphoric acid, or 3-O-methyl-D-[14C]glucose. These studies demonstrate that RO 2-2985 enhances the efflux of calcium microinjected into the proximal portions of the rat nephron.
A model for transepithelial fluid transport
Authors: Bresler E. H.
Published: December 2017

A number of experimental observations which are not easily, or at all, accommodated within the framework of the natriocentric theory for transepithelial fluid transport are discussed. These are shown to be not merely accommodated but actually predicted by a simple model for fluid transport in which the major osmotic force leading to fluid transport derives from solutes other than NaCl. The model is then analyzed for feasibility in light of existing data relating to reflection coefficients for NaCl and hydraulic conductivity. Certain lines of evidence for specific active sodium transport are critically reexamined.
Effects of AVP and DDAVP on plasma renin activity and electrolyte excretion in conscious dogs
Authors: Johnson M. D. , Kinter L. B. , Beeuwkes R.
Published: December 2017

Uninephrectomized adult female dogs with chronic indwelling catheters were maintained on a low sodium diet and studied without anesthesia. Following hydration with 3% dextrose, an intravenous infusion of either arginine vasopressin (AVP) or of 1-desamino-8-D-arginine vasopressin (DDAVP) was begun. The dose was calculated to achieve a near maximal physiological plasma concentration of AVP, or an equimolar concentration of DDAVP. Both AVP and DDAVP increased urinary osmolality from less than 60 to over 800 mosmol/kg H2O within 1 h. AVP infusion increased mean arterial pressure and renal electrolyte excretion and decreased heart rate and plasma renin activity (PRA), while DDAVP was without effect on these parameters. AVP infused into the renal artery at doses which did not alter systemic pressure and heart rate caused kaliuresis and reduced PRA. We conclude that the AVP-induced inhibition of renin secretion and increase in renal electrolyte excretion are not secondary to increased tubular permeability to water, but must represent a more specific action of AVP which is not shared by DDAVP.
Luminal influences on potassium secretion: sodium concentration and fluid flow rate
Authors: Good D. W. , Wright F. S.
Published: December 2017

Two methods of in vivo continuous microperfusion were used to evaluate separately luminal sodium concentration and fluid flow rate as factors regulating potassium secretion by the renal distal tubule of the rat. Emphasis was placed on evaluating changes in sodium concentration (43-97 mM) and flow rate (4-27 nl/min) within the physiological range. Absolute rates of Na, K, Cl, and H2O transport were measured. Results showed that increasing early distal flow rate without increasing early distal Na concentration significantly increased the absolute rate of potassium secretion by the distal tubule. In contrast, increasing early distal Na concentration, distal Na delivery, and distal Na absorption did not affect potassium secretion if flow rate was not changed. Further studies showed that reducing early distal Na concentration below the physiological range (to 15 mM) caused the direction of net sodium transport to be reversed but did not significantly reduce potassium secretion. Increasing early distal K concentration (to 34 mM) caused the direction of net potassium transport to be reversed. The rate of potassium secretion appears to depend in part on the luminal potassium concentration. Increases in luminal flow rate may increase the rate of potassium secretion by lowering the luminal K concentration.
Determination of liver intracellular pH in vivo and its homeostasis in acute acidosis and alkalosis
Authors: Park R. , Leach W. J. , Arieff A. I.
Published: December 2017

An in vivo method is presented for the determination of liver intracellular pH (pHi) using [14C]dimethadione (DMO) in dogs. This method differs from those previously published in that hepatic venous and portal venous blood pH were selected as the extracellular reference pH, and liver blood space corrections are applied to whole liver tissue [14C]DMO activity. Using these corrections, a normal liver pHi of 6.99 +/- 0.03 (SE) was obtained. During acute metabolic acidosis and alkalosis, as well as during acute respiratory acidosis and alkalosis, the liver pHi remained normal; metabolic acidosis was 7.04 +/- 0.04; metabolic alkalosis was 6.92 +/- 0.08; respiratory acidosis was 6.98 +/- 0.04; and respiratory alkalosis was 7.00 +/- 0.10. None of these values was significantly different from normal (P greater than 0.05). Changes in intracellular bicarbonate and lactate appeared to account in part for the observed stability of the liver pHi despite acute manipulations resulting in a range of pH values between 7.09 and 7.63 in arterial blood.
Potassium secretion along the inner medullary collecting duct
Authors: Bengele H. H. , McNamara E. R. , Alexander E. A.
Published: December 2017

Potassium transport along the inner medullary collecting duct (IMCD) was evaluated by the microcatheterization technique in Charles River CD (cesarean derived) rats 7-9 days after sham operation (S) or uninephrectomy (UNPX). The fraction of filtered potassium (TF/P)K/In) as a function of IMCD length was analyzed by linear regression. In 13 S rats there was a significant correlation and slope (P less than 0.001) and (TF/P)K/In increased from 14% at the beginning of the IMCD to 25% in the urine. IMCD potassium secretion accounted for about half of the excreted potassium. In the UNPX rats a significant correlation and slope was also obtained (P less than 0.001); (TF/P)K/In at the beginning of IMCD was 24% and increased to 36% in the urine. No difference in slope was noted between the groups. There was a slightly greater absolute potassium secretion after UNPX (0.77 +/- 0.03 S vs. 0.93 +/- 0.04 mueq/min UNPX), but this did not account for most of the difference in potassium excretion noted. We conclude that net potassium secretion occurs along the IMCD in S and UNPX rats. After UNPX, there is significantly greater potassium delivery to the IMCD and a greater kaluresis. The increased kaluresis cannot be accounted for primarily by increased potassium secretion along the IMCD.
Dissociation of proximal tubular glucose and Na+ reabsorption by amphotericin B
Authors: Aronson P. S. , Hayslett J. P. , Kashgarian M.
Published: December 2017

The effect of amphotericin B on glucose and Na+ transport was studied in the Necturus proximal tubule and in microvillus membrane vesicles isolated from the rabbit renal cortex. In the Necturus experiments, the rate constants for disappearance of radiolabeled glucose (kG) and mannitol (kM) from the tubular lumen were determined by stop-flow microperfusion. Saturability and Na+-dependence of glucose reabsorption was confirmed, since kG was reduced by raising intratubular glucose from 1 to 5 mM or by replacing intratubular Na+ with choline. Neither maneuver affected kM. Intratubular amphotericin B (10 microgram/ml), previously shown to stimulate active Na+ reabsorption in the Necturus proximal tubule, inhibited kG with no effect on kM. In the membrane vesicle preparation, amphotericin inhibited the uphill glucose uptake which results from imposing a NaCl gradient from outside to inside, but had no effect on glucose uptake in either the absence of Na+ or in the presence of Na+ when there was no Na+ gradient. Amphotericin B stimulated the uptake of Na+ by the vesicles. The observed dissociation of glucose and Na+ transport by amphotericin B is consistent with the concept that proximal tubular glucose reabsorption is energized by the luminal membrane Na+ gradient and is not directly linked to active Na+ transport per se.
Effects of intraluminal D-glucose and probenecid on urate absorption in the rat proximal tubule
Authors: Knight T. F. , Senekjian H. O. , Sansom S. , Weinman E. J.
Published: December 2017

The in vivo microperfusion technique was employed to examine urate absorption in the proximal convoluted tubule of the rat kidney using [2–14C]urate as the marker for fractional urate absorption. With NaCl as the perfusion solution, water absorption averaged 2.53 +/- 0.16 nl.min-1.mm tubule-1, and the fractional absorption of [2–14C]urate averages 11.6 +/- 1.0%/mm tubule. The addition of D-glucose (50 mg/100 ml) enhanced water absorption to 3.62 +/- 0.19 nl.min-1.mm tubule-1, but inhibited fractional urate absorption to 6.6 +/- 1.2%/mm tubule. Phloridzin (4.4 mg/100 ml), 2-deoxy-D-glucose (45.6 mg/100 ml), and 3-O-methyl-D-glucose (53.9 mg/100 ml) also inhibited the absorption of [2–14C]urate to the same degree as did D-glucose despite differing effects on water absorption. The addition of probenecid (2.8 mg/100 ml) to the NaCl perfusion solution had no effect on water absorption but inhibited [2–14C]urate absorption to 6.4 +/- 0.6%/mm tubule. The addition of both probenecid and phloridzin further reduced [2–14C-A1urate absorption to 3.8 +/- 0.7%/mm tubule. Probenecid alone had no effect on glucose transport. These studies suggest that the presence of either certain hexose sugars, phloridzin, or probenecid in the lumen of the proximal convoluted tubule inhibits the tubular absorption of urate.
Renin secretion during dynamic changes in renal perfusion pressure
Authors: Blaine E. H. , Zimmerman M. B.
Published: December 2017

Uninephrectomized ewes were prepared with a renal artery flow probe and catheters were implanted into the renal artery, vein, and ureter. The renal perfusion pressure (RPP) of conscious animals was decreased externally by 13 +/- 3, 21 +/- 3, 31 +/- 3 mmHg over 5 min and returned to control levels over 5 min. Reduction of RPP by 13 and 21 mmHg resulted in prompt increases in renin secretion (RS) which were maximal coincident with the nadir of the downward ramp (delta RS 195 +/- 43 P less than 0.05, and 1,077 +/- 208 ng AI/min, P less than 0.01, respectively). Directly measured renal blood flow (RBF) was not decreased and no measurable change occured in GFR. When RPP was reduced by 31 mmHg, RBF and GFR were decreased and renin secretion rose further (delta RS 1,480 +/- 384 AI/min, P less than 0.05). On the upward pressure ramp, RS fell promptly and was nearly at control levels upon restoration of RPP. It was concluded that renin secretion responds rapidly to alterations in RPP in the autoregulatory range and these changes in renin secretion are unlikely to be mediated by a tubular receptor.