bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism of arginine by the isolated perfused rat kidney
Authors: Perez G. O. , Epstein M. , Rietberg B. , Loutzenhiser R.
Published: December 2017

In order to evaluate the renal contribution to the metabolism of arginine, we have evaluated its biosynthesis and catabolism in the isolated perfused rat kidney. The kidneys of eight male Sprague-Dawley rats were perfused with Krebs-Ringer-bicarbonate buffer containing albumin and amino acids. Twenty-five muCi of L-[guanidino-14C]arginine or 25 muCi L-[guanidino-14C]citrulline were added to the system and radiochromatograms of the perfusate were obtained at 0, 30, 60, and 90 min. Perfusate levels of urea, creatine, and guanidine derivatives were measured with high-pressure liquid chromatography. During perfusion there was net utilization of arginine and net production of creatine, guanidinoacetic acid (GAA) and guanidinosuccinic acid (GSA). The guanidino carbon of arginine was incorporated by the kidney into urea, creatine GSA, GAA, and guanidinobutyric acid. The production of 14C-labeled urea from L-[guanidino-14C]citrulline was substantially lower than that previously demonstrated in the liver, while that of arginine was approximately 20 times greater. These studies demonstrate the important contribution of the kidney to the synthesis and metabolism of arginine.
Mechanism of exaggerated diuresis in spontaneously hypertensive rats
Authors: DiBona Gerald F. , Rios Linda L.
Published: December 2017

The mechanism of exaggerated diuresis and natriuresis was studied in spontaneously hypertensive rats (SHR) by renal clearance and micropuncture techniques. Control normotensive rats of the same age and sex [Wistar-Kyoto rats (WKY)] were also studied. During the hydropenic control and the volume-expansion experimental periods absolute and fractional water and sodium excretion were greater in SHR than in WKY. Although fractional and absolute water and sodium reabsorption were similar along the proximal convolution in SHR and WKY, fractional and absolute water reabsorption in Henle's loop was less in SHR than in WKY. Hydrostatic and colloid osmotic pressures in the cortical peritubular microvasculature were similar in WKY and SHR. Acute normalization of renal perfusion pressure by aortic constriction reversed the exaggerated diuresis and natriuresis in SHR by halving the filtered load of water and sodium; whole kidney and single nephron glomerular filtration rates and blood flows decreased by 50%. It is concluded that the exaggerated diuresis and natriuresis of the spontaneously hypertensive rat is caused by a decreased reabsorption in the loop of Henle. The mechanism of this decreased reabsorption in the loop of Henle cannot be explained by alterations in the measured physical forces in the renal cortical microvasculature.

natriuresis; autoregulation; volume expansion

Submitted on November 15, 1977

Accepted on June 7, 1978
Immunohistochemical localization of the prostaglandin-forming cyclooxygenase in renal cortex
Authors: Smith W. L. , Bell T. G.
Published: December 2017

An immunohistofluorescence procedure for detecting prostaglandin-forming cyclooxygenase has been used to localize the enzyme in the renal cortex of the cow, guinea pig, rabbit, rat, and sheep. Cyclooxygenase antigenicity was found in endothelial cells lining all arteries and arterioles and in cortical collecting tubules in each species examined. The enzyme was also detected in epithelial cells of Bowman's capsule in the rabbit and in mesangial cells in both ovine and bovine glomerular tufts. That prostaglandins can be formed in renal resistance vessels suggests that it is the synthesis occurring in these vessels which is responsible for the effects of prostaglandins on renal blood flow. Of further note is the correlation that exists between the location of the cyclooxygenase and that of the antidiuretic hormone-responsive adenyl cyclase in the distal nephron.
Effect of ouabain and colloid osmotic pressure on renal tubule cell volume
Authors: Linshaw M. A. , Stapleton F. B.
Published: December 2017

Proximal renal tubule cell volume increases in ouabain but cell swelling is limited by the tubule basement membrane (TBM) and the colloid osmotic pressure from the bath protein. We compared the effect of ouabain, external protein concentration, and TBM on cell volume of proximal convoluted (PCT), proximal straight (PST), and cortical collecting tubules (CCT). We blocked active solute transport with ouabain and evaluated cell size by measuring the outer diameter of nonperfused tubules. Proximal tubules in ouabain swelled 35–40% in isoncotic medium and 20–25% further in hyponcotic medium (0.3 g/100 ml albumin), but PCT swelled faster than PST. The CCT swelled minimally in similar mediums, indicating pronounced heterogeneity in the response of cortical nephron segments to ouabain. In the presence of ouabain, all tubules swelled extensively when we removed the TBM with collagenase. In the hyponcotic medium fluid flux across the peritubular membrane was 0.081, 0.049, and 0.030 nl/min per mm tubule length for PCT, PST, and CCT, respectively. The rates of fluid flux in PCT and PST were proportional to estimates of the respective basolateral surface areas. We suggest that differences in swelling rates between proximal segments reflect variations in surface area rather than intrinsic peritubular membrane permeability to solute and water.
Renal histamine H1 and H2 receptors: characterization and functional significance
Authors: Banks R. O. , Fondacaro J. D. , Schwaiger M. M. , Jacobson E. D.
Published: December 2017

Canine experiments were designed to determine if both histamine H1 and H2 receptors are present in the renal circulation. Renal blood flow (RBF) increased steeply over the first minute of intra-arterial histamine infusion, then increased gradually to a plateau in 3– –5 min. Infusion of either histamine + H2 antagonist or of H1 agonist produced the initial rapid increase in RBF, whereas infusion of either histamine + H1 antagonist or of H2 antagonist produced a slower but more sustained increase in RBF. Histamine significantly increased urine flow rate (V), chloride excretion, and glomerular filtration rate (GFR). Infusion of the H2 agonist also increased V and Cl excretion without affecting GFR. By contrast H1 agonist significantly reduced V and Cl excretion and tended to reduce GFR (P less than 0.1 greater than 0.05). Histamine, H1 agonist, and H2 agonist each increased inner cortical more than outer cortical blood flow. These data suggest that 1) H1 and H2 receptors are present in the renal vasculature, 2) changes in intrarenal blood flow distribution are not responsible for histamine-induced diuresis, and 3) H1 receptors are primarily postglomerular while H2 receptors exhibit both pre- and postglomerular distribution.
Effect of exogenous and endogenous angiotensin II in the isolated perfused rat kidney
Authors: Davalos M. , Frega N. S. , Saker B. , Leaf A.
Published: December 2017

Rat kidneys were perfused with an artificial solution at constant pressure. The infusion of angiotensin II (AII) (1.5––6 ng min-1) reduced renal perfusate flow (RPF) from 36.6 +/- 2.4 to 19.3 +/- 1.4 ml min-1 (P less than 0.001) (n = 13); GFR rose from 0.48 +/- 0.06 to 0.63 +/- 0.04 ml min-1 (P less than 0.05), and filtration fraction (FF) rose accordingly from 0.015 +/- 0.002 to 0.033 +/- 0.003 (P greater than 0.01). The same results were obtained with purified renin substrate (synthetic tetradecapeptide, 100 ng min-1, n = 8); RPF fell from 31.5 +/- 2.9 to 17.2 +/- 2 ml min-1 (P less than 0.001), GFR rose from 0.36 +/- 0.05 to 0.51 +/- 0.04 ml min-1 (P less than 0.05), and FF increased from 0.021 +/- 0.002 to 0.034 +/- 0.006 (P less than 0.01). The effects of renin substrate were completely prevented by the converting enzyme inhibitor SQ 20,881 (3 X 10(-5) M). In another six experiments the effects of renin substrate at the same dose were fully reversed by addition of the analogue [Sar1,Ala8]AII. We interpret these findings to indicate that both exogenous and endogenous AII produce preferential vasoconstriction of the efferent arteriole, increasing the driving force for ultrafiltration and thereby maintaining or increasing GFR in the face of a reduced plasma flow.
Fluoride tissue distribution: short-term kinetics
Authors: Whitford G. M. , Pashley D. H. , Reynolds K. E.
Published: December 2017

The short-term distribution kinetics of 18F, with and without added carrier, were studied in 12 soft tissues and femur following intravenous administration in rats. The animals were killed in groups of four at 5, 10, 15, 20, 30, and 60 min after the dose. A tissue was judged to be kinetically homogeneous with plasma if an early and constant tissue water-to-plasma (T/P) 18F concentration ratio was established. In the carrier-free study, liver, heart, skin, fat, and kidney met this criterion. In the presence of carrier, four other tissues were added to this group. Brain, resting skeletal muscle, spleen, and femur did not achieve constant T/P values. The addition of carrier resulted in significantly lower T/P ratios in nine tissues. This was especially marked in femur. It is concluded that 1) none of the soft tissues studied strongly binds 18F; 2) most of these tissues are kinetically homogeneous with plasma; and 3) the presence of carrier fluoride can significantly influence the kinetic behavior and distribution of 18F. Finally, based on the current and previously reported 18F T/P ratios, and on reported intracellular-extracellular pH gradients, it is hypothesized that fluoride distribution in several soft tissues is determined by the diffusion equilibrium of HF, that is, by the magnitude of the transmembrane pH gradient.
Measurement of oxygen consumption in voltage-clamped epithelia
Authors: Lang M. A. , Rosenthal S. J. , Caplan S. R. , Essig A.
Published: December 2017

Standard apparatus for in vitro study of anuran epithelia was adapted for the incorporation of Clark oxygen electrodes, permitting the concurrent measurement of electrical current (active sodium transport) and oxygen consumption under voltage-clamp conditions, with independent manipulation of the two bathing solutions. Stability was enhanced by electrical isolation of the O2 electrodes, sensitive temperature control (+/- 0.03 degrees C), and constancy of stirring rate. Mean rate of drift was less than 3.7% of the average rate of basal (i.e., nontransport related) O2 consumption. In the present configuration the response time was less than 15 s. Visual fitting of slopes of O2 tension evaluated rates of O2 consumption with adequate accuracy in the physiological range (basal rates averaged about 20 pmol-s-1-cm-2 toad bladder, corresponding to about 10 pmol-s-1-mg-1 dry wt, or about 5 pmol-s-1-ml-1 chamber volume). Rpresentative slopes were read with a standard deviation of 3.5%.
Effective luminal hypotonicity: the driving force for isotonic proximal tubular fluid absorption
Authors: Andreoli T. E. , Schafer J. A.
Published: December 2017

This Editorial Review summarizes certain considerations relevant to the mechanism(s) of isotonic fluid absorption by the mammalian proximal nephron. Recent evidence indicates that the paracellular pathway in this epithelium has a low diffusion resistance. Therefore it is possible that lateral intercellular spaces are in diffusion equilibrium with the peritubular medium. For such a circumstance, the driving forces for isotonic fluid absorption may reside in external solutions. But since the hydraulic conductance of mammalian proximal tubules is remarkably high, the effective osmotic pressure gradient between luminal and pertibular solutions required to drive isotonic fluid transport is relatively small. In the mammalian proximal nephron, effective luminal hypotonicity may provide the driving force for isotonic fluid transport. At least two mechanisms could account for the development of effective luminal hypotonicity. First, preferential absorption of bicarbonate results in a rise of luminal Cl- concentration. And because proximal tubules are more permeable to Cl- than to HCO3-, there develops a driving force for isotonic fluid transport. Second, trivial degrees of luminal hypotonicity may develop attendant on active Na+ absorption. We provide evidence that, of these two mechanisms, axial anion asymmetry is the dominant force for isotonic fluid transport.
A new needle-type colloid osmometer for continuous determination of blood oncotic pressure
Authors: Kakiuchi Y. , Arai T. , Horimoto M. , Kikuchi Y. , Koyama T.
Published: December 2017

For the purpose of facilitating measurement of colloid osmotic pressure of body fluids, a new needle-type colloid osmometer which uses a hollow fiber as a semipermeable membrane instead of a sheet ultrafilter was developed. The simple construction, easy production, and satisfactory performance of the osmometer are described in detail. Although hydrostatic pressure existing in the sample interfered a little with the accuracy of measurement, quickly interchangeable sensing probes brought great advantages in practice.
Inhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMP
Authors: Sahib M. K. , Schwartz J. H. , Handler J. S.
Published: December 2017

Page F586: M. K. Sahib, J. H. Schwartz, and J. S. Handler. “Inhibition of toad urinary bladder sodium transport by carbamylcholine: possible role of cyclic GMP.” In Table 3 (page F589) the values 11.9 ± 0.6 for cAMP and 0.28 ± 0.02 for cGMP should be opposite 10 mU/ml AVP plus 100 μM carbamylcholine. Braces have been added to the table to define the paired experiments. The corrected table follows.

(See PDF)
Phosphate transport along the inner medullary collecting duct of the rat
Authors: Bengele H. H. , Lechene C. P. , Alexander E. A.
Published: December 2017

The question of phosphate transport along the collecting duct remains controversial inasmuch as no data from direct in vivo evaluation of this nephron segment have been reported. We measured net phosphate transport along the inner medullary collecting duct (IMCD) using the collecting duct microcatheterization technique in five groups of rats. In control rats no net phosphate transport was found and 9.4% of the fraction of filtered phosphate (FFP) entered the IMCD and was excreted. After acute thyroparathyroidectomy (TPTX) there was a striking reduction in the FFP entering the IMCD, 1.8%, and significant reabsorption occurred, 0.5% being excreted. With acute TPTX and parathormone infusion, delivery increased to 33% without significant change along the IMCD. With acute TPTX and phosphate infusion, delivery was increased to control levels but no change was found in net phosphate transport. In rats studied 5-7 days after uninephrectomy alone, phosphate delivery was greater than in control, 25%, and no net phosphate transport was found. These studies demonstrate that phosphate absorption occurs along the IMCD in acutely TPTX rats when the delivery of phosphate to the IMCD is markedly reduced. The increase in phosphaturia which occurs after a reduction in renal mass cannot be accounted for by changes in net phosphate transport along the IMCD.
Determination of Na-K-ATPase activity in single segments of the mammalian nephron
Authors: Doucet A. , Katz A. I. , Morel F.
Published: December 2017

A micromethod for the determination of Na-K-ATPase in discrete segments of nephrons from rabbit, rat, and mouse kidneys is described. To facilitate tubule microdissection, the kidneys were perfused with collagenase after it had been verified that collagenase had no effect on ATPase activity. Individual tubule segments were dissected under stereomicroscopic observation, exposed to a hypotonic environment followed by rapid freezing, and incubated in 1 microliter assay medium. Enzyme activity was determined by direct measurement of labeled inorganic phosphate release by the hydrolysis of [gamma-32P]ATP and was expressed as a function of tubule length. This method is technically simple enough to permit simultaneous measurement of the enzyme in large numbers of tubules and sufficiently sensitive to determine its activity in each region of the nephron. Correlation of Na-K-ATPase activity in single tubules with functional measurements obtained in the corresponding segment of the nephron with the perfused tubule or micropuncture techniques should help define the role of this enzyme in tubular ion transport.
Na-K-ATPase activity along the rabbit, rat, and mouse nephron
Authors: Katz A. I. , Doucet A. , Morel F.
Published: December 2017

Na-K-ATPase activity along the rabbit, rat, and mouse nephron was determined with a micromethod that measures directly labeled phosphate released by the hydrolysis of [gamma-32P]ATP. Na-K-ATPase activity was highest in the rat, intermediate in the mouse, and lowest in the rabbit nephron. With the exception of rabbit cortical thick ascending limb, the enzyme profile was similar in the three species: Na-K-ATPase activity per millimeter tubule length was highest in the distal convoluted tubule and thick ascending limb of Henle's loop, intermediate in the proximal convoluted tubule, and lowest in the pars recta and collecting tubule. The enzyme was present in the thin limbs of Henle's loop, but its activity was very low and measurements were close to the sensitivity limit of the method. Both the absolute activity and the fraction of the total enzyme represented by Na-K-ATPase were severalfold higher than in kidney homogenates. Finally, the Na-K-ATPase activity measured in certain segments of the rat and rabbit nephron in this study seems sufficient to account in theory for the active component of the net sodium transport found in the corresponding region of the nephron with either in vivo or in vitro single tubule microperfusion techniques.
Corticoid effects on angiotensin- and norepinephrine-induced proteinuria in rats
Authors: Bauman J. W.
Published: December 2017

Adrenalectomy is known to prevent the proteinuria induced by renin or angiotensin, but it is not clear whether the loss of glucocorticoids or mineralocorticoids is responsible. The problem was reinvestigated using dexamethasone and aldosterone, essentially pure glucocorticoid and mineralocorticoid, respectively. Dexamethasone treatment for 2––5 days completely restored the protein-uric response to angiotensin II or norepinephrine, but aldosterone did not, even though the dose and treatment were sufficient to induce changes in electrolyte excretion. Fractional sodium excretion was also increased by angiotensin II and norepinephrine in the dexamethasone-treated rats, but not in the aldosterone-treated rats. Both dexamethasone and aldosterone treatments restored the increase in filtration fraction, but the increase was not associated with proteinuria in some groups, and it is concluded that there is no causal relationship between increased filtration fraction and proteinuria. Reasons for considering binding of norepinephrine and angiotensin to the glomerular basement membrane as causal for the proteinuria and the hormonal requirements for such binding are discussed.
Secretion of prostaglandin E2 by rabbit proximal tubules
Authors: Irish J. M.
Published: December 2017

This study was designed to evaluate prostaglandin secretion from bath to urine in isolated perfused rabbit proximal tubules. Active prostaglandin E2 (PGE2) secretion occurred along the entire length of the proximal tubule, but the rate of net secretion was highest in the S2 segment of the proximal straight tubule. Sixteen percent of the PGE2 secreted in the proximal straight tubule was metabolized to other products. The PGE2 cell-to-bath ratio averaged 40 and the tubule fluid-to-bath ratio averaged 3.4. These findings suggest active transport of PGE2 across the peritubular membrane and passive movement across the luminal membrane. Indomethacin, probenecid, para-aminohippurate, and ouabain partially inhibited PGE2 cell accumulation and net secretion. PGE2 entered the urine of the perfused descending limb of Henle (DLH), but at a rate two orders of magnitude below that observed in the S2 segment of the proximal tubule. No evidence of active PGE2 secretion was observed in the DLH. These results suggest that PGE2 is secreted into the urine at substantial rates by the organic anion transport system of renal proximal tubules.
p-Aminohippuric acid transport into brush border vesicles isolated from flounder kidney
Authors: Eveloff J. , Kinne R. , Kinter W. B.
Published: December 2017

p-Aminohippuric acid (PAH) transport was investigated in brush border vesicles isolated from renal proximal tubules of the winter flounder. Three characteristics of carrier-mediated transport were demonstrated: 1) unlabeled PAH inhibited the uptake of [3H]PAH; 2)[3H]PAH efflux from the vesicles was stimulated in the presence of unlabeled PAH in the extravesicular medium; and 3) PAH influx was inhibited by 2,4-dinitrophenol (DNP) and 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene (SITS). D-Glucose plus a sodium gradient stimulated PAH uptake, as did a K2SO4 gradient plus valinomycin, suggesting that PAH is transported as an anion. In contrast, PAH uptake into a membrane fraction containing mainly basal-lateral plasma membranes exhibited a larger inhibition by probenecid but a smaller inhibition by unlabeled PAH and SITS. Thus, carrier-mediated transfer of PAH driven by the electrochemical potential difference for PAH is demonstrated in the brush border membrane of the flounder kidney.
Renal autoregulation of blood flow and filtration rate in the rabbit
Authors: Ott C. E. , Vari R. C.
Published: December 2017

Electromagnetic flow techniques and inulin clearance were used to determine the autoregulatory capabilities of the rabbit kidney in vivo. Renal blood flow was measured in 13 animals over a renal perfusion pressure range of 40–110 mmHg. Normal renal blood flow averaged 3.2 +/- 0.3 ml.min-1.g kidney-1 and was efficiently autoregulated above a renal artery pressure of 75 mmHg. For every 10 mmHg renal pressure change above 75 mmHg renal blood flow changed only 0.96%. Renal perfusion pressure was reduced from 102 +/- 3 to 74 +/- 2 mmHg in six animals. Over this pressure range glomerular filtration rate was not significantly decreased and averaged 4.2 +/- 0.5 ml/min at high pressure compared to 4.0 +/- 0.5 ml/min at low perfusion pressure. Results show that the rabbit kidney autoregulates renal blood flow and glomerular filtration rate efficiently above 75 mmHg. This range of autoregulation compares well with the autoregulatory range of the dog. The results also show that in the autoregulatory range the rabbit and the rat appear to autoregulate with equal efficiency but that the rabbit kidney begins to autoregulate at a low perfusion pressure than the average of approximately 100 mmHg usually found in the rat.
Two modes of phosphate transport by turtle urinary bladder
Authors: Johnson J. P. , Green S. , Schwartz J. H.
Published: December 2017

The effects of changes in pH and addition of CO2/HCO3- on transepithelial phosphate transport were studied in turtle urinary bladder. Net mucosa-to-serosa flux of phosphate (JP) was determined as the difference between unidirectional 32P fluxes in the absence of transepithelial electrochemical gradients. With 5 mM phosphate in HCO3--free Ringer at pH 8.4, JP was 21.8 +/- 7.4 nmol . 8 cm-2 . h-1. There was a slight increase in JP with isohydric addition of 10 mM HCO3-. Addition of 5% CO2, which reduced pH to 7.3, did not affect JP. At pH 8.4, JP was not affected by ouabain or dinitrophenol and increased progressively as phosphate concentration was raised between 0.5 and 10 mM. At pH 6.2 in the absence of exogenous CO2 and HCO3-, JP was undectable. With 2.5 mM HCO3- and 5% CO2 at pH 6.5, JP was 61.3 +/- 16.0 and decreased to 30.6 +/- 1.6 nmol . 8 cm-2 . h-1 when pH was raised to 7.2 by increasing HCO3- to 10 mM. At pH 6.5 JP was inhibited by both ouabain and dinitrophenol. These results suggest that at acidic pH, JP results from the tranport of H2PO4-. The transport of H2PO4- is CO2 dependent and inhibited by ouabain and dinitrophenol. In contrast, at alkaline pH, JP results from the transport of HPO4(2-), which is neither CO2 dependent nor inhibited by ouabain or dinitrophenol.
Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions
Authors: Rosenberg G. A. , Kyner W. T. , Estrada E.
Published: December 2017

Although bulk flow of brain interstitial fluid (ISF) occurs with changes in hydrostatic and osmotic pressures, under normal conditions only diffusion of molecules in the ISF has been reported. Extrachoroidal cerebrospinal fluid (CSF) production and intracerebral injection studies, however, provide indirect evidence for the bulk flow of ISF under normal conditions. We studied tissue penetration profiles of an extracellular molecule in gray and white matter after 1-, 2-, 3-, and 4-h ventriculocisternal perfusions. Gray matter apparent diffusion coefficients were similar at different times as expected with diffusion; however, white matter coefficients decreased significantly with time, suggesting bulk flow of ISF. White matter data was reanalyzed for both bulk flow and diffusion; we calculated a diffusion coefficient of 3.00 x 10(-6) cm2/s and a velocity for ISF of 10.5 micrometers/min toward the ventricle. Additional animals were given 20% mannitol (1.5--3 g/kg) intravenously prior to a /-h ventriculocisternal perfusion. Mannitol produced a significant bulk flow of ISF away from the ventricle in gray matter. We estimate that 30% of extrachoroidal CSF production is from flow of ISF in white matter.
Effects of alterations in urine flow rate on prostaglandin E excretion in conscious dogs
Authors: Kirschenbaum M. A. , Serros E. R.
Published: December 2017

The relationships between urinary prostaglandin E excretion and urine flow rate were evaluated in 11 conscious mongrel dogs during antidiuresis, maximal water loading, vasopressin administration during maximal water loading, and mannitol infusion. Urine flow rates between 0.21 and 15.1 ml/min were achieved. Urinary prostaglandin E excretion rates, determined by a membrane receptor assay, varied directly with urine flow rates (r = 0.908). Vasopressin administration (34--540 microU . kg-1 . min-1) resulted in a fall, rather than the expected rise, in urinary prostaglandin E excretion. When the concentration of prostaglandin E in the urine was plotted against urine flow rate, the demonstrated relationship appeared most consistent with passive diffusion. Mannitol infusion increased urine flow rates to levels comparable to the levels seen with maximal water loading but did not result in a fall in plasma osmolality. Urinary prostaglandin E excretion rates, however, were not distinguishable from those in the previous group. These data demonstrate that urinary prostaglandin E excretion rates are determined, to a great extent, by urine flow rate and that the significance of the interpretation of elevated excretion levels of these lipids in diuretic states may have to be reevaluated.
Relationship between renal fluid and Mg secretion in a glomerular marine teleost
Authors: Renfro J. L.
Published: December 2017

Renal tubular fluid secretion has been studied in seawater-acclimated winter flounder, Pseudopleuronectes americanus. Although this animal has a filtration kidney and a relatively high glomerular filtration rate (GFR = 1.35 ml . kg-1 . h-1), apparently more than half of the final urine volume was secreted fluid, and net fluid secretion was frequently observed. The dominant divalent ion excreted in the urine was Mg, of which 98% was secreted. A strong correlation (r = 0.98) was seen between secreted Mg and the rate of tubular fluid secretion. The calculated concentration of Mg in secreted fluid was 169 mM, a figure that was substantiated by values obtained for urine Mg concentration when urine flow was due almost entirely to tubular fluid secretion. Alterations in urine flow rate reflected changes in the rate of Mg secretion; however, no correlation was seen between GFR and secreted Mg, which may indicate independence of renal portal blood flow and glomerular blood flow. No relationship between Mg secretion and sodium reabsorption was apparent. These observations support the hypothesis that Mg secretion together with accompanying anions (Cl and SO4) accounts entirely for tubular fluid secretion in the winter flounder.
Renal interstitial pressure and sodium excretion during renal vein constriction
Authors: Burnett J. C. , Knox F. G.
Published: December 2017

Studies were performed on anesthetized dogs to determine the relationship of interstitial pressure to sodium excretion during renal vein constriction in the presence and absence of volume expansion. Renal interstitial pressure was measured from implanted capsules during basal renal venous pressure and increased pressures of 10, 20, 30, and 40 mmHg. A positive relationship between renal venous pressure and interstitial pressure was demonstrated in hydropenia and in volume expansion, with markedly higher interstitial pressures obtained in volume expansion. A positive correlation was demonstrated between fractional sodium excretion and renal interstitial pressure in hydropenia as compared to a significant negative correlation in volume expansion. Negative correlations were demonstrated in volume expansion between renal interstitial pressure and glomerular filtration rate and renal blood flow as compared to no significant change in these parameters in hydropenia. Accordingly, a positive correlation was demonstrated between renal interstitial pressure and sodium excretion in hydropenia but not in volume expansion. Volume expansion was characterized by higher interstitial pressure and decreased sodium excretion in association with decreased renal blood flow and glomerular filtration rate.
Mechanism of activation of renal Na+-K+-ATPase in the rat: effects of potassium loading
Authors: Rodriguez H. J. , Hogan W. C. , Hellman R. N. , Klahr S.
Published: December 2017

The mechanism of activation of Na+-K+-ATPase after chronic potassium loading has been investigated in the rat kidney. Potassium loading stimulated the specific activity of Na+-K+-ATPase in the cortex and medulla of the kidney. This effect was not accompanied by a generalized increase in the cellular contents of RNA and proteins and could not be accounted for by an effect of potassium loading on renal growth. Enzyme induction does not appear to be mediated by changes in the endogenous levels of glucocorticoid or thyroid hormones. Evidence obtained from investigation of the partial reactions (Pi intermediate, ouabain-sensitive pNPPase) of the Na+-K+-ATPase enzymatic reaction is consistent with the interpretation that chronic potassium loading in the rat increases the number of enzyme units (Na+ pumps) in the cortex of the kidney. Analysis of the kinetic parameters (Km, K1/2, Vmax, Hill coefficients) of the enzymatic reaction indicates that K+ loading has little or no effect on the kinetic properties (affinity, cooperativity) of the stimulated transport enzyme.
Glomerular adaptations to chronic dietary salt restriction or excess
Authors: Schor N. , Ichikawa I. , Brenner B. M.
Published: December 2017

Micropuncture studies were performed in 33 Munich-Wistar rats maintained chronically either on dietary NaCl restriction (group 1) or excess (group 2). Values for single nephron (SN) and total kidney glomerular filtration rate (GFR) were identical in both groups. Nevertheless, because of preferential efferent vasoconstriction, glomerular capillary hydraulic pressure (PGC) was higher in group 1, offsetting the lower initial glomerular plasma flow rate (QA) also found in group 1. The pressor response to infusion of exogenous angiotensin II (AII) was less in group 1 than in group 2, suggesting that vascular receptors for AII may have been occupied by endogenous hormone, the latter leading to the efferent arteriolar vasoconstriction. In addition to AII, prostaglandins also appear to be involved in the adaptations of the glomerular microcirculation to chronic variations in salt intake. In group 1, indomethacin or meclofenamate infusion mimicked exogenous AII, causing declines in QA and SNGFR. These changes were lacking in group 2. Because of relative contraction of plasma volume, the vasodilatory effects of prostaglandins appear to be needed in low salt animals to sustain SNGFR and QA. In the high salt group, however, since plasma volume is not contracted, maintenance of SNGFR and QA appears to be less critically dependent on endogenous prostaglandins.
Significance of comparative studies for renal physiology
Authors: Dantzler W. H.
Published: December 2017

Comparative studies contribute significantly to determining principles of renal physiology. Examples of comparative relationships important for past, current, or future studies are discussed. Structural simplicity of the avian glomerulus may permit detailed analysis of filtration pressure profiles. Alterations in nephron function, redistribution of filtration among nephron populations, and control by antidiuretic hormone and other factors are readily demonstrable in nonmammalian vertebrates. Studies of the distal tubule-glomerular feedback mechanism may be particularly revealing in nephrons of nonmammalian vertebrates, many of which lack a macula densa. The influence of volume flow rate in collecting ducts on the concentrating mechanism can be analyzed readily in avian kidneys in which glomerular intermittency influences such flow. The structure of Henle's loops may be related to the importance of sodium, chloride, and urea in avian and mammalian concentrating mechanisms. Perfusion of isolated reptilian renal tubules to study urate transport has also raised questions about fluid absorption and may permit more detailed analysis of some other transport systems than perfusion of mammalian tubules. Simplicity of some nonmammalian systems and exaggerated functions in these systems should continue to make them useful for revealing basic principles of renal function.
Sodium and chloride transport along the inner medullary collecting duct: effect of saline expansion
Authors: Bengele H. H. , Lechene C. , Alexander E. A.
Published: December 2017

The effect of volume expansion on inner medullary collecting duct (IMCD) sodium transport remains controversial. Studies employing micropuncture of the IMCD base and tip were interpreted to demonstrate enhanced sodium and chloride reabsorption. Data obtained by microcatheterization evaluating only sodium transport revealed either no reabsorption or net addition. We have examined both sodium and chloride transport by microcatheterization. Volume expansion was comparable to the micropuncture studies: 0.9% saline equal to 10% body wt and then matched to urine flow. The fraction of filtered fluid, sodium, and chloride was analyzed as a function of IMCD length. In eight hydropenic rats 60% of the fluid, 71% of the sodium, and 48% of the chloride delivered to the IMCD was reabsorbed. In six volume-expanded rats no significant net reabsorption of fluid, sodium, or chloride was found. Accordingly, in contrast to the micropuncture results, we have demonstrated that net sodium chloride and fluid reabsorption are absent during volume expansion. We conclude that during volume expansion, fluid, sodium, and chloride excretion increase, in part, because of a reduction in net reabsorption along the IMCD. The degree of volume expansion does not account for the discrepancy between the two techniques.
Prevention of maleate-induced tubular dysfunction by acetoacetate
Authors: Szczepanska M. , Angielski S.
Published: December 2017

Maleate administration produces features that closely resemble the Fanconi syndrome. To determine whether this dysfunction is caused by maleate or its metabolite, maleyl-CoA, which is produced in the succinyl-CoA transferase reaction, the effect of pretreatment with acetoacetate on the maleate dysfunction was tested in rats, Infusion of acetoacetate, 90 mu mol . min-1 . kg body wt-1 protects the kidney from maleate action, whereas administration of propionate, a monocarboxylic anion and CoA-dependent metabolite resembling the anion of acetoacetate, has no effect on maleate-induced renal dysfunction. Maleate (100 mg/kg body wt) alone lowered kidney ATP concentration by 44%, whereas maleate with acetoacetate did not prevent the decreased renal ATP (42%), while glucosuria, phosphaturia, calciuria, and bicarbonaturia were significantly diminished. Similar changes in renal ATP level were observed in rats treated with propionate or propionate and maleate in combination. These experiments demonstrate that maleate per se is not inhibitory but that its metabolite, presumably maleyl-CoA, may inhibit tubule function.
Renal vascular resistance and reactivity in the neurogenic hypertensive rat
Authors: Fink G. D. , Bryan W. J.
Published: December 2017

Increased sympathetic nervous system activity in the kidney has been postulated as a possible etiologic factor in some forms of hypertension. The present investigation sought to document the possibility of a chronic increase in neurogenic renal vasoconstriction in an experimental model in which increased nervous activity would be expected--neurogenic hypertension resulting from partial baroreceptor deafferentation. In anesthetized rats with chronic neurogenic hypertension, renal vascular resistance was significantly higher than in sham-operated rats. After acute renal denervation, there was no statistically significant difference in renal vascular resistance between the two groups. Thus, a chronic increase in neurogenic renal vascular resistance was apparent in the hypertensive rats. Since renal vascular responses to direct renal nerve activation, norepinephrine, and other exogenous vasoactive hormones were not altered in the hypertensive rats, the increased neurogenic vasoconstriction was probably the result of increased renal nerve discharge. Unaltered neurotransmission and reactivity further indicated a failure of the renal nerves or blood vessels to "adapt" to increased nervous activity. These results support previous suggestions that increased renal sympathetic nerve activity could result in sustained neurogenic renal vasoconstriction and thereby contribute to the development of hypertension.
Vasopressin and collecting duct intramembranous particle clusters: a dose-response relationship
Authors: Harmanci M. C. , Stern P. , Kachadorian W. A. , Valtin H. , DiScala V. A.
Published: December 2017

Vasopressin increases the permeability of collecting ducts to water. Administration of this hormone is also associated with an increase in intramembranous particle clusters in rat collecting duct luminal membrane (CDLM) as revealed by freeze-fracture electron microscopy. To determine whether this morphologic alteration of CDLM is quantitatively related to the dose of vasopressin, anesthetized Brattleboro homozygous rats were given the hormone at different doses. CDLM from kidneys removed before and during infusion were examined by freeze-fracture electron microscopy. The frequency of CDLM clusters as well as the area of membrane occupied by them was related to the dose of vasopressin. In a separate experimental protocol, a decrease in intramembranous particle clusters accompanied a decrease in urinary osmolality when vasopressin was stopped. We conclude that CDLM intramembranous particle clusters represent a specific structural change related to the action of vasopressin. Accordingly, quantitation of CDLM clusters may serve as an end point for the study of vasopressin-induced water permeability.
Effect of glucose on renal excretion of electrolytes in the rat
Authors: Roy D. R. , Seely J. F.
Published: December 2017

Glucose ingestion or infusion increases calcium and magnesium excretion in the human. To assess the role of renal tubular glucose reabsorption and of the parathyroid glands in this phenomenon, we performed standard two-phase clearance experiments in fed, volume-expanded male Sprague-Dawley rats. When compared with a group of animals receiving only 0.9% NaCl (group I), animals infused with glucose (group II) excreted significantly more calcium at any given level of sodium excretion (delta FECa, 1.95 +/- 0.24 vs. 0.69 +/- 0.18, P < 0.001). Normoglycemic hyperinsulinemia (group III) did not reproduce this increase in calcium excretion. In the group given phloridzin during sustained hyperglycemia (group IV), calcium excretion was well below that of control animals at any given level of sodium excretion. The glycosuric-hyperglycemia group (group V) used to assess the effect of glycosuria seen in group IV responded with a striking calciuria (delta FECa, 3.31 +/- 0.43, P < 0.001, compared with group IV). TPTX animals responded to glucose in the same way as intact animals (delta FECa, 4.8 +/- 0.5 vs. 2.18 +/- 0.3 in TPTX saline controls, P < 0.001). Magnesium excretion in all groups followed the same pattern as calcium. We conclude that renal tubular glucose reabsorption is essential for glucose to augment calcium and magnesium excretion. The presence of the parathyroid glands was not required for this phenomenon to occur.
Glucocorticoid receptors in rat kidney cortical tubules enriched in proximal and distal segments
Authors: Mishina T. , Scholer D. W. , Edelman I. S.
Published: December 2017

Cytoplasmic and nuclear binding of [3H]triamcinolone acetonide was assessed in isolated rat kidney cortical tubules, enriched in distal (fraction A) or in proximal segments (fraction B). The concentration dependence of specific [3H]triamcinolone acetonide binding in cytoplasm was determined (range = 4.4 X 10(-10) to 2.1 X 10(-7) M) and analyzed by a least-squares curve-fitting method. A single, high-affinity binding class with a dissociation constant of 1 X 10(-8) M (25 degrees C) was obtained in both fractions A and B. Based on competition for the [3H]triamcinolone acetonide sites, the following sequence of affinities was obtained: triamcinolone acetonide = dexamethasone > progesterone = corticosterone > d-aldosterone > 17 beta-estradiol. These specificities imply that these sites are glucocorticoid receptors. Fraction B contained 1.6 times more cytosol sites for [3H]triamcinolone acetonide than fraction A (5.0 +/- 0.5 X 10(-13) vs. 3.0 +/- 0.5 X 10(-13) mol/mg protein). In the presence of a onefold excess of d-aldosterone specific cytoplasmic binding of [3H]triamcinolone acetonide was 1.4-fold greater in fraction B than in fraction A, and specific nuclear binding was 1.3-fold greater in fraction B than in fraction A (5.1 +/- 0.6 X 10(-13) vs 4.0 +/- 0.5 X 10(-13) mol/mg DNA). These results and the measured lengths of proximal and distal tubules yielded estimates of a higher proximal content (three- to sixfold) compared to distal content of glucocorticoid receptors.
Dissociation of tubuloglomerular feedback responses from distal tubular chloride concentration in the rat
Authors: Bell P. D. , McLean C. B. , Navar L. G.
Published: December 2017

Previous studies have demonstrated that stop-flow pressure (SFP) feedback responses can occur during orthograde perfusion with solutions having low amounts of sodium or chloride. However, retrograde perfusion studies have suggested a specific role for chloride concentration in mediating feedback responses. These studies were conducted to compare SFP feedback responses during orthograde and retrograde perfusion with an artificial tubular fluid solution (ATF) (Cl- = 135 meq/liter) and a Na+ isethionate solution (Cl- = 6 meq/liter). With ATF, increases in perfusion rate from 10 to 35 nl/min led to decreases in SFP of 11 +/- 1.4 mmHg, increases in distal tubular fluid Cl- of 46 +/- 4.9 meq/liter, and osmolality of 58 +/- 10 mosmol/kg. There were significant inverse relationships between SFP and changes in Cl- and osmolality. With Na+ isethionate, SFP decreased by 8.4 +/- 1.0 mmHg, osmolality increased by 43 +/- 8 mosmol/kg, and Cl- did not change. There was a significant relationship between SFP and osmolality, but not with Cl-. During retrograde perfusion at 15 nl/min, SFP decreased by 12 +/- 1.2 mmHg with ATF and by 12 +/- 1.2 mmHg with Na+ isethionate. These results demonstrate that feedback-mediated decreases in SFP can occur in the absence of concomitant increases in distal Cl- and suggest that the receptor system does not have a unique and specific requirement for chloride.
Determination of disequilibrium pH in the rat kidney in vivo: evidence of hydrogen secretion
Authors: DuBose T. D. , Pucacco L. R. , Carter N. W.
Published: December 2017

The recent demonstration of elevated PCO2 in structures of the rat renal cortex indicated that previous determinations of disequilibrium pH (pHDq), and thus the differentiation of H+ secretion from bicarbonate reabsorption per se, required further evaluation. A new aspiration pH electrode was developed to allow tubule fluid to achieve chemical equilibrium at the PCO2 prevailing in vivo. In control and bicarbonate-loaded rats a pHDq was not observed in either proximal or distal tubules. After intravenous benzolamide a significant acid pHDq was observed in the proximal (but not the distal) nephron, and increased further during metabolic alkalosis. During combined metabolic alkalosis and respiratory acidosis a significant pHDq was present in the distal but not in the proximal tubule. Aldosterone administration to bicarbonate-loaded, hypercapnic rats did not alter the distal pHDq further. When present, the pHDq in the distal tubule was obliterated by carbonic anhydrase infusion. We conclude that proximal but not distal tubule fluid is in functional contact with carbonic anhydrase; the enzyme is in excess in the proximal lumen and H2CO3 did not accumulate even during conditions associated with increased H+ secretion; the basal rate of H+ secretion in the distal nephron accessible to cortical micropuncture is less than previously assumed. The data support the view that H+ secretion is the major mechanism of renal bicarbonate reabsorption.
Evidence for active and passive urate transport in the rat proximal tubule
Authors: Weinman E. J. , Senekjian H. O. , Sansom S. C. , Steplock D. , Sheth A. , Knight T. F.
Published: December 2017

Studies utilizing the technique of simultaneous microperfusion of peritubular capillaries and tubular lumen of the proximal tubule of the rat were performed to determine if the absorption of urate was an active transport process and to determine the passive permeability coefficient for urate. When radioactive urate of equal specific activity and concentration was present in both perfusion solutions, the ratio of collected to initial concentrations of urate in the luminal perfusate (CO/CI) was 0.71 +/- 0.02. This gradient was higher than that predicted at equilibrium from the electrical potential difference determined in the in vitro perfused rabbit proximal tubule. The addition of para-chloromercuribenzoate (PCMB) to both solutions resulted in a significantly higher CO/CI of 0.90 +/- 0.02. This latter value is closer to the value predicted at electrochemical equilibrium. In separate studies, the unidirectional fluxes of urate were determined in the presence of PCMB. The calculated passive permeability coefficient averaged approximately 0.94 pmol . min-1 . mm-1 . mM-1 and was equal in both directions. These results indicate that in the rat proximal tubule urate absorption is an active transport process. In addition, there exists a passive permeation pathway for urate movement out of and into the proximal tubule.