bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated actions of renal medullary prostaglandins in the control of water excretion
Authors: Stokes J. B.
Published: December 2017

The renal medulla is a rich source of prostaglandins. Two cell types, the collecting tubule epithelium and the interstitial cell, have the enzymatic machinery necessary to make prostaglandins. As a result of this localized production and the proximity to highly specialized medullary structures, the prostaglandins can exert potent effects on several aspects of medullary function. At least three physiologic effects have been clearly documented: reduction of vasopressin-dependent osmotic water permeability of the collecting tubule epithelium, enhancement of medullary blood flow, and inhibition of NaCl absorption from the thick ascending limb of Henle's loop. These three functions are the functions that primarily regulate axial solute content and water excretion. The effect of increasing medullary prostaglandin production is to reduce medullary solute content and increase water excretion. Each action in this regard. The medullary prostaglandins thus antagonize the ultimate action of vasopressin. In addition to the direct antagonistic effect on vasopressin-dependent osmotic water flow across the collecting tubule, prostaglandins and vasopressin may have antagonistic effects at other sites. These actions of medullary prostaglandins provide an integrated mechanism for the "fine tuning" of water excretion.
Drug-induced papillary necrosis: electrolyte excretion and nephron heterogeneity
Authors: Sabatini S. , Mehta P. K. , Hayes S. , Kurtzman N. A. , Arruda J. A.
Published: December 2017

The functional expression of papillary necrosis was investigated in rats following administration of 2-bromoethylamine hydrobromide (BEA). The percentage of filtering superficial and juxtamedullary nephrons was assessed using the qualitative Hanssen technique. There was a marked decrease in the percentage of filtering juxtamedullary nephrons 24 h after the induction of papillary necrosis (as compared with control rats), which was blunted in salt-loaded animals. The percentage of filtering superficial nephrons was the same in all three groups. BEA administration to normal rats was associated with a significant increase in sodium, chloride, phosphate, and calcium excretion. BEA administration to rats on a chloride-restricted diet was associated with chloride wastage. These animals also failed to adapt to a low chloride diet as late as 7 days after the administration of BEA. The phosphaturia observed in intact rats treated with BEA was abolished by parathyroidectomy. BEA-treated rats were able to adapt to a low phosphate diet and to a low magnesium diet. These data demonstrate that papillary necrosis is associated with profound impairment of juxtamedullary nephron filtration and with chloride wastage. In the absence of the papillary structures adaptation to phosphorus or magnesium deprivation is still possible.
Measurement of nephron filtration in the dog: role of proximal intratubular pressure
Authors: Hartupee D. A. , Gillies A. H. , Knox F. G.
Published: December 2017

Previous studies concerning the measurement of single nephron filtration rate have shown that collections of proximal tubular fluid, in which an oil drop is held in a constant position, do not affect intratubular pressure in the early proximal tubule in the hydropenic rat. Since intratubular pressures are higher in the dog than the rat, we investigated the effect of position-controlled collections on proximal pressure and single nephron filtration rate (SNGFR) in the dog. During position-controlled collections, early proximal pressure fell 5.8 +/- 0.9 mmHg and SNGFR was 76.3 +/- 5.3 nl/min. During proximal re-collections, in which proximal pressure was maintained near the free-flow value using a long immobile oil block, SNGFR was significantly less, 44.4 +/- 5.5 nl/min. For each micropunctured kidney, SNGFR was also estimated by dividing GFR by the number of glomeruli (mean, 5.4 +/- 0.5 X 10(5)). Estimated SNGFR (50.9 +/- 6.3 nl/min) was not significantly different from pressure-controlled SNGFR but was significantly less than position-controlled SNGFR. Accordingly, in the dog, early proximal pressure decreases during position-controlled collection of proximal tubular fluid, resulting in an overestimation of SNGFR. This artifact can be avoided by controlling the intratubular pressure during collection of tubular fluid.
Short-term effect of aldosterone on Na-K-ATPase in single nephron segments
Authors: Doucet A. , Katz A. I.
Published: December 2017

One of the theories proposed to explain the action of mineralocorticoids on target tissues attributes their effect on cation transport to stimulation of the “sodium pump.” To test this hypothesis we evaluated the short-term effect of aldosterone on Na-K-ATPase in discrete nephron segments microdissected from kidneys of adrenalectomized animals. Na-K-ATPase activity measured in proximal and distal nephron segments from adrenalectomized as well as intact mice remained unchanged 1 or 3 h after a single injection of D-aldosterone (10 micrograms/100 g body wt i.p.). Similarly, no effect of aldosterone could be demonstrated in experiments in vitro, in which tubules from adrenalectomized mice and rabbits were incubated (90 min, 37 degrees C) in the presence of physiologic or pharmacologic concentrations of the hormone (3.10(-10) to 3.10(-6) M). These studies did not show an effect of aldosterone on isolated tubule Na-K-ATPase within the time interval in which this hormone alters tubular cation transport and therefore do not support the “pump theory” of mineralocorticoid action.
Renal tubular transport and metabolism of organic cations by the rabbit
Authors: Besseghir K. , Pearce L. B. , Rennick B.
Published: December 2017

The renal tubular transport of the organic cations tetraethylammonium (TEA), N1-methylnicotinamide (NMN), and choline was studied in anesthetized rabbits by the urinary clearance technique. The clearance ratio of [14C]TEA/inulin was 5.72 +/- 0.44 and the clearance ratio of [14C]TEA/p-aminohippuric acid (PAH) was 0.98 +/- 0.02. The clearance ratio of the 14C label/inulin when [14C]NMN was being infused was only 1.31. The clearance ratio of choline/inulin was less than 1 at choline infusion loads from 0 to about 6 mumol . kg-1 . min-1, which produced a plasma choline level of 100 microM. At higher infusion rates the urinary clearance ratio of choline/inulin rose to a maximum of 2 at plasma choline levels of 300–500 microM. Renal metabolism of choline and NMN were revealed by the use of the isolated perfused rabbit kidney. [14C]Choline was extensively metabolized by the kidney into betaine. The renal metabolite of [14C]NMN comigrated with nicotinamide in electrophoresis. The relatively low urinary clearance of the label associated with NMN in the rabbit presents a striking difference from its transport in dog and rat. Studies using isolated perfused segments are done using tissue from rabbits primarily. These data from the intact rabbit kidney may be used to guide future studies of organic cation transport with isolated perfused segments.
Differences in active and passive glucose transport along the proximal nephron
Authors: Barfuss D. W. , Schafer J. A.
Published: December 2017

The transport of D-glucose was examined in isolated perfused segments of the rabbit proximal nephron. The total unidirectional lumen-to-bath flux of D-glucose in rabbit proximal convoluted tubules (PCT) and early and late segments of proximal straight tubules (PST) could be described as the sum of two independent fluxes: one due to an active saturable transport site and the other a parallel passive permeation pathway. Both fluxes increased with increasing perfusion rate as a result of increased average luminal glucose concentration. The maximal active transport rate for glucose decreased along the nephron from 83.2 pmol . min-1 . mm-1 in the PCT to 12.9 and 7.9 in the early and late PST, respectively. The Km value for the active site also decreased from 1.64 mM in the PCT to 0.70 and 0.35 in the early and late PST, respectively. The permeability value for the passive permeation pathway, which was assessed from the linear dependence of bath-to-lumen fluxes of L-glucose on bath concentration, decreased from 0.033 micrometers/s in the PCT to 0.015 and 0.009 in the early and late PST, respectively. These characteristics of a high transport capacity with moderate leak in the PCT and lower transport capacity with low leak in the PST allow the establishment of steep glucose concentration gradients in the PCT that are maintained and augmented in the late proximal nephron.
Effect of furosemide on calcium and magnesium transport in the rat nephron
Authors: Quamme G. A.
Published: December 2017

Superficial tubules were perfused in vivo to determine the effect of intraluminal furosemide on electrolyte transport in the loop of Henle and distal tubule of the rat with special reference to calcium and magnesium reabsorption. in vivo perfusion of single tubules allowed us the opportunity to investigate separate electrolyte transfers with altering the corticomedullary concentration gradient within the kidney. Intraluminal furosemide (3 X 10(-6) and 3 X 10(-5) M) resulted in proportionately greater calcium and magnesium inhibition relative to sodium and chloride in Henle's loop. Furosemide had little effect on transport function within the perfused superficial distal tubule. Distal calcium and magnesium reabsorption was dependent on their respective deliveries to this segment. Parathyroid hormone increased fractional calcium and magnesium reabsorption in Henle's loop and the distal tubule in the presence of intraluminal furosemide. These results are consistent with a luminal effect of furosemide in the loop of Henle that inhibits calcium and magnesium transport to a greater degree than sodium chloride. Intraluminal ethacrynic acid (10(-4) M) or its cysteine complex had no effect on electrolyte transport in the perfused rat nephron.
Amiloride inhibition of the Na+-H+ exchanger in renal microvillus membrane vesicles
Authors: Kinsella J. L. , Aronson P. S.
Published: December 2017

We examined the effect of amiloride on Na+-H+ exchange in rabbit renal cortical microvillus membrane vesicles. Amiloride inhibited both the uphill Na+ accumulation induced by imposition of a transmembrane Hin+ greater than Hout+ gradient and the uphill H+ efflux induced by imposition of a Naout+ greater than Nain+ gradient. The inhibitory effect of amiloride on Na+ influx was rapidly reversible and fully competitive (Ki 3.0 X 10(-5) M amiloride, KT 6.3 mM Na+). In addition, amiloride inhibited the efflux of Na+ from vesicles preloaded with Na+. However, the diuretic did not inhibit such other Na+-coupled transport processes as Na+-glucose ad Na+-alanine cotransport. These findings suggest that amiloride is a reversible, selective, competitive inhibitor for the Na+ site of the renal microvillus membrane Na+-H+ exchanger. Amiloride may, therefore, be useful as an experimental tool for investigating the role of Na+-H+ exchange in mediating proximal tubular acidification.
Plasma level and renal handling of Pi: effect of overnight fasting with and without Pi supply
Authors: Trohler U. , Bonjour J. P. , Fleisch H.
Published: December 2017

Overnight fasting significantly increases plasma inorganic phosphate ([Pi]p) in rats previously fed low Pi diet (LPD), whereas it slightly decreases [Pi]p in rats previously fed high Pi diet (HPD). We assessed the role of the kidney in these differing responses by investigating the influence of overnight fasting on renal tubular capacity to reabsorb Pi by clearance technique in conscious rats. To also evaluate the effect of Pi deprivation during overnight fasting three groups of animals were studied: fed, completely fasted, and fasted with a Pi supply in the drinking water. In intact LPD and HPD rts the tubular Pi reabsorptive capacity was not different between fed and completely fasted rats. It was, however, found to be lower in fasted but Pi-supplied than in fed animals, indicating a decrease by overnight fasting with respect to all nutrients except Pi, i.e., by fasting per se. Conversely, it was higher in the animals completely fasted than in those fasted but Pi-supplied, showing an increase by overnight Pi deprivation. These two opposite effects explain the absence of any significant influence of overnight complete fasting on tubular Pi handling. The same results were obtained in thyroparathyroidectomized rats on low Pi intake. This study shows that the kidney can adapt its transport capacity for Pi according to changes in Pi supply within 12 h. It also suggests that it may react by a decrease in reabsorption to the reduction in Pi utilization that can be expected to occur during fasting per se. Furthermore, our data explain how the kidney, by adapting its tubular Pi transport to the prior dietary intake of Pi, can account for the difference in phosphatemic response to overnight fasting and consequently in the diurnal fluctuation of [Pi]p observed between LPD and HPD animals.
Isolated perfused salamander proximal tubule. II. Monovalent ion replacement and rheogenic transport
Authors: Sackin H. , Boulpaep E. L.
Published: December 2017

Early proximal tubules of the salamander kidney (Ambystoma tigrinum) were isolated and perfused in vitro. Transepithelial and basolateral electrical potential differences, transepithelial resistances, and intracellular ionic activities were measured during removal of Na+, K+, or Cl- from the lumen, the bath, or both lumen and bath. The effects of these external ionic replacements are interpreted in terms of an equivalent circuit that represents the renal epithelium as a network of passive ionic resistances, ionic diffusion potentials, and active transport current sources. Results indicate that rheogenic transport across the basolateral membrane is substantially diminished by removal of Na+ from either lumen or bath or by removal of K+ from the bath. On the other hand, bilateral chloride removal produces an increase in transepithelial resistance but almost no change in the calculated rate of basolateral rheogenic transport. This suggests that the source of the basolateral rheogenic ion flux ia a Na-K-ATPae that actively transports an excess of outward Na+ over inward K+.
Decreased luminal membrane transport of phosphate in chronic renal failure
Authors: Hruska K. A. , Klahr S. , Hammerman M. R.
Published: December 2017

To examine the effects of the hyperparathyroidism that accompanies chronic renal failure (CRF) on Pi transport across the renal proximal tubular luminal membrane, brush border membrane vesicles (BBMV) were prepared from the viable portion of the kidney of dogs with CRF or normal renal function. Initial rates of Na+ gradient-dependent Pi transport were decreased in BBMV from dogs with CRF compared with normal dogs. Initial rates of 22Na+ uptake in BBMV from dogs with CRF, however, were increased, suggesting a more rapid dissipation of the Na+ gradient in these vesicles. Initial rates of Pi transport measured under Na+-equilibrated conditions were decreased in BBMV from dogs with CRF. Parathyroidectomy of dogs with CRF abolished this decrease in Pi uptake. We conclude that the adaptations in Pi excretion associated with CRF are accompanied by changes in Na+-dependent Pi transport in BBMV and, therefore, possibly across the luminal membrane of the renal tubule. Moreover, the activity of this transport system can be altered by parathyroidectomy of dogs prior to isolation of BBMV.
Aldosterone binding in isolated tubules II. An autoradiographic study of concentration dependency in the rabbit nephron
Authors: Farman N. , Vandewalle A. , Bonvalet J. P.
Published: December 2017

Specific binding of aldosterone along the rabbit nephron was investigated using an autoradiographic method on microdissected tubules within a large range of [3H]aldosterone ([3H]A) concentrations (3 X 10(-10) to 2 X 10(-8) M). Paired incubations with [3H]A in the presence or absence of unlabeled A (100-fold excess) were done to determine the specific binding. In addition, competition studies (10 times excess) with A, dexamethasone (Dex), and estradiol (E) were performed. No specific nuclear binding was detected in the proximal convoluted tubule and pars recta. In the cortical collecting tubule (CCT), a high specific labeling occurred at concentrations of A as low as 3 X 10(-10) M that plateaued at 1.5 X 10(-9) M. Aldosterone was the best competitor. In the bright and granular distal tubule, the binding resembled that of CCT, but Dex was nearly as potent a competitor as A. All along the loop of Henle and in the medullary collecting duct, the binding of A was weak at low concentrations and gradually rose with concentration without reaching a plateau. An almost equivalent displacement was obtained by A and Dex in 10-fold excess. We conclude that aldosterone binds mostly to mineralocorticoid sites in the collecting tubule, whereas the binding appears to be to both mineralo- and glucocorticoid sites in the distal tubule, in the different parts of the loop of Henle, and in the medullary collecting tubule.
Toad bladder compliance and water permeability in response to stretch
Authors: Eggena P.
Published: December 2017

The pressure/volume relationship of toad urinary bladders was measured from 0 to 50 cmH2O. Optimal bladder capacity was derived by extrapolation of the pressure/volume curve to a pressure of 0 cmH2O. The compliance of the bladder wall was calculated from the slope of the pressure/volume curve at intraluminal pressures above 10 cmH2O. Neither vasopressin nor atropine had any effect on bladder wall compliance. Bladders filled with one-fifth strength Ringer fluid and suspended in full-strength Ringer lost weight at 0.02 (at half-optimal capacity), 0.08 (at optimal capacity), and 0.26 mg.min-1.cm-2 (at supra-optimal capacity, 25 cmH2O) in the absence of vasopressin. With 20 mU/ml vasopressin, bladders lost weight at 1.08 (at half-optimal capacity), 1.55 (at optimal capacity), and 1.74 mg.min-1.cm-2 (at supra-optimal capacity, 25 cmH2O). When bladder wall tension was raised from 2,102 to 28,383 dyn/cm, the permeability to [14C]mannitol increased from 8 X 10(-7) to 39 X 10(-7) cm/s. Electron microscopy of bladders fixed at a wall tension of 17,572 dyn/cm showed flattening of the microvilli, rupture of the apical cell membranes of some granular and mitochondria-rich epithelial cells, but no obvious alteration in the tight junctions. This study suggests that stretching the apical plasma membrane to the point at which it ruptures in some cells does not alter the capacity of vasopressin to induce its characteristic increase in permeability to water of this membrane.
Neural and extraneural catecholamine production by rat kidneys
Authors: Stephenson R. K. , Sole M. J. , Baines A. D.
Published: December 2017

Catecholamine production by innervated kidneys was examined by radioenzymatic assay of norepinephrine (NE), epinephrine (E), and dopamine (DA) in lymph, urine, arterial plasma, and renal venous plasma of hydropenic rats. Denervation reduced NE excretion in urine by 18% and both NE and DA efflux in renal venous plasma by 37 and 30%, respectively. The kidney's handling of E was unaltered by denervation. Renal nerves added 1.0 +/- 0.2 ng/min to the efflux of NE in urine and renal venous plasma. Denervation reduced this efflux to -0.1 +/- 0.2 ng/min. DA efflux from innervated kidneys was 1.4 +/- 0.2 ng/min but only half came from renal nerves, as denervated kidneys released 0.7 +/- 0.1 ng/min. Renal lymph from innervated kidneys contained slightly more NE but less DA than arterial plasma. We conclude that renal nerves release both NE and DA but that half of the renal contribution to urine and renal venous plasma DA efflux comes from extraneuronal tissue. Renal lymph NE and DA concentrations are similar to those in arterial plasma, suggesting that peritubular concentrations are low everywhere except within renal clefts.
Determinants of proximal bicarbonate, chloride, and water reabsorption during carbonic anhydrase inhibition
Authors: Cogan M. G. , Rector F. C.
Published: December 2017

To examine the magnitude and load dependency of proximal reabsorption during carbonic anhydrase inhibition with acetazolamide, Munich-Wistar rats were studied in hydropenia and following an increase in single nephron glomerular filtration rate (SNGFR) by either plasma or colloid-free Ringer expansion. During acetazolamide administration, when plasma loading increased SNGFR 50% compared with hydropenia, total CO2, chloride, and water proximal reabsorption rose proportionally, so that fractional proximal reabsorption rates remained constant (0.20-0.27). When SNGFR was comparably increased with Ringer expansion, total CO2, chloride, and water reabsorption were decreased relative to their respective rates during plasma expansion and, in fact, were not changed compared with hydropenic values. At all flow rates during carbonic anhydrase inhibition, end-proximal total CO2 and chloride concentrations were only slightly higher than in the glomerular ultrafiltrate, so that reabsorption was isohydric. In further studies, proximal reabsorption remained isohydric when the glomerular ultrafiltrate bicarbonate concentration was reduced in metabolic acidosis. In conclusion, absolute proximal reabsorption of bicarbonate, chloride, and water during carbonic anhydrase inhibition 1) proceeds isohydrically, with minimal anion concentration gradients generated, over a wide range of filtered loads, and 2) can be flow dependent (with plasma loading) as well as modulated by peritubular protein concentration, even though passive chloride transport is minimized.
Relationship among gluconeogenesis, QO2, and Na+ transport in the perfused rat kidney
Authors: Silva P. , Hallac R. , Spokes K. , Epstein F. H.
Published: December 2017

The relationship among sodium transport (TNa), oxygen consumption (QO2), and gluconeogenesis was studied in isolated perfused rat kidneys in which glucose formation was enhanced by providing pyruvate as a substrate and by prior treatment with methylprednisolone. TNa was increased abruptly by increasing perfusion pressure as to increase GFR or by lowering the albumin concentration of a hyperoncotic perfusate as to allow glomerular filtration to occur. Increases in TNa of 40% were accompanied by little or no increase in QO2, whereas gluconeogenesis decreased 55-80%. Conversely, a decrease in perfusion pressure that lowered TNa produced an increase in glucose formation without a change in QO2. When gluconeogenesis was blocked with 0.15 mM 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, QO2 increased together with TNa as perfusion pressure was raised. The results suggest that the energy needed for ion transport by the kidney may under some circumstances be borrowed from nontransport functions and, therefore, that basal oxygen consumption may vary with the rate of reabsorptive transport.
Acidification of luminal fluid by the rabbit cortical collecting tubule perfused in vitro
Authors: Koeppen B. M. , Helman S. I.
Published: December 2017

The ability of the rabbit cortical collecting tubule to acidify the luminal fluid was determined with double-barreled antimony pH electrodes. In Na+/K+ Ringer the tubules maintained a transepithelial voltage (VToc) of -45.4 +/- 5.5 mV (bath grounded) and a minimum luminal fluid pH of 5.93 +/- 0.11. Chronic mineralocorticoid pretreatment of the rabbits caused the VToc to become more negative (-78.7 +/- 8.2 mV) and decreased the minimum luminal fluid pH to 5.43 +/- 0.16. In most tubules (control and mineralocorticoid-pretreated) the measured pH was more acidic than could be accounted for by either the lumen-negative VToc or CO2 equilibration of the perfusion fluid. When tubules were perfused and bathed in 0 Na+/0 K+ Ringer they developed a lumen-positive VToc, which was stimulated by mineralocorticoid, was sensitive to the PCO2 of the bathing solutions, but was not dependent on Cl- in either the luminal or bath solutions. Luminal acidification in the absence of Na+ and K+ (pH = 6.05 +/- 0.12) occurred against a lumen-positive VToc of +11.5 +/- 1.9 mV. Addition of 10(-4) M ouabain to the bath of tubules studied in Na+/K+ Ringer caused the VToc to reverse polarity and the luminal fluid pH to increase. In contrast, ouabain had no effect on either the lumen-positive VToc or the minimum luminal fluid pH when added to the bath of tubules in 0 Na+/0 K+ Ringer. Bath addition of 10(-4) M acetazolamide and/or 5 X 10(-4) M 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) caused alkalinization of the luminal fluid in tubules studied in either Na+/K+ or 0 Na+/0 K+ Ringer. In 0 Na+/0 K+ Ringer, acetazolamide and SITS reduced the lumen-positive VToc to near zero. The data support the existence of a distinct acidification mechanism in the rabbit cortical collecting tubule, which is both active and electrogenic.
Relationship between plasma potassium concentration and renal potassium excretion
Authors: Young D. B.
Published: December 2017

To study the relationship between extracellular potassium concentration and renal excretion of potassium, seven chronically adrenalectomized dogs were maintained on a constant intravenous infusion of aldosterone (50 micrograms/day), and constant sodium intake (30 meq/day ) while they received four levels of potassium intake--10, 30, 100, and 200 meq/day--for 7-10 days each. At the conclusion of each level of intake, plasma potassium and renal excretion as well as other variables known to influence potassium excretion were measured. There were minimal changes in arterial pH, mean arterial pressure, extracellular fluid volume, or glomerular filtration rate at any level of potassium intake. The values for plasma potassium and renal potassium excretion attained at each level of intake were: 3.13 +/- 0.24 and 10 +/- 2; 4.18 +/- 0.18 and 21 +/- 6; 4.31 +/- 0.11 and 66 +/- 10; and 4.75 +/- 0.10 meq/liter and 170 +/- 16 meq/day, respectively. Under these experimental conditions in which the levels of aldosterone, sodium intake, arterial pH, arterial pressure, extracellular fluid volume, and glomerular filtration rate remain constant, plasma potassium concentration appears to have a week effect on renal potassium excretion below the normal level of plasma potassium (approx. 11 meq/day change in excretion for each milliequivalent per liter change in concentration). Above the normal level, however, plasma potassium concentration has a powerful effect, 260 meq/day per milliequivalent per liter. The characteristics of the relationship between plasma potassium and renal potassium excretion make it ideally suited for controlling potassium excretion in response to greater than normal potassium intake.
Tubular handling of Pi in young growing and adult rats
Authors: Caverzasio J. , Bonjour J. P. , Fleisch H.
Published: December 2017

The tubular transport of inorganic phosphate (Pi) is controlled by a parathyroid hormone-independent mechanism that responds to variations in the Pi intake. This adaptation mechanism could also respond to growth-mediated variation in the utilization of Pi by the organism. In the present work we have determined the maximal net Pi reabsorption per volume of glomerular filtrate (max TRPi/ml GF) in the young growing (2-mo) and adult 8- to 9-mo) rats. Max TRP[i/ml GF was significantly lower in intact adult (1.44 +/- 0.06 mumol/ml) compared with intact young growing animals (2.22 +/- 0.12 mumol/ml GF). This difference was maintained after removal of the thyroparathyroid glands; adult, 2.89 +/- 0.25, young, 4.56 +/- 0.25 mumol/ml. It was not associated with a difference in the urinary excretion of cAMP, GFR, renal handling of sodium, plasma calcium, or acid-base status. Administration of growth hormone preparations to adult rats did not raise max TRPi/ml GF to the level observed in young intact animals. With regard to the tubular Pi adaptation to Pi restriction, lowering the phosphorus content in the diet from 0.8 to 0.2 g/100 g resulted in an attenuated and delayed enhancement in max TRPi/ml in adult as compared with the response observed in young growing rats. These results show that the decrease in tubular reabsorption of Pi that occurs when rats become adult in a parathyroid hormone-independent phenomenon. It is suggested that this change is an adaptation of the tubular Pi transport to a reduction in the utilization of Pi in relation to the diminished growth rate of the animals.
Amino acids enhance renal tubular absorption of the los-molecular-weight proteins insulin and growth hormone
Authors: Rabkin R. , Gottheiner T. I. , Tsao T. S.
Published: December 2017

The effect of amino acids(AA) on the tubular absorption of low-molecular-weight (LMW) proteins was studied in isolated rat kidneys. Kidneys were perfused with an albumin-electrolyte solution that contained insulin or human growth hormone (hGH) and, unless otherwise stated, the following L-amino acids: glycine, isoleucine, serine, alanine, methionine, proline, arginine, and aspartic acid. In kidneys perfused without AA, fractional urinary insulin clearance (FCi) averaged 7.4 +/- 1.54%, whereas in the presence of multiple AA the FCi was significantly lower (0.68 +/- 0.2%, P less than 0.01). Addition of glycine or alpha-aminoisobutyric acid (AIB) alone also reduced the FCi significantly (1.79 +/- 0.66 and 1.59 +/-1.06%, respectively). By contrast, perfusion with the other AA individually did not alter the FCi. The fractional urinary hGH clearance was also significantly lower in kidneys perfused with multiple AA (0.94 +/- 0.47%) than in those perfused without AA (9.07 +/- 1.2%). We conclude that tubular absorption of filtered insulin and hGH is enhanced by the presence of AA. The mechanism is unclear, but enhancement of insulin absorption can be produced by glycine and AIB alone. This raises the possibility of a link between the absorption of insulin and the glycine and AIB shared transport system, but excludes a primary metabolic effect because AIB is nonmetabolizable.
H+-dependent sulfate secretion in the marine teleost renal tubule
Authors: Renfro J. L. , Pritchard J. B.
Published: December 2017

Renal sulfate secretion was studied in the southern flounder Paralichthys lethostigma. In the intact animal sulfate clearance averaged 12 times the glomerular filtration rate and about 93% of the excreted sulfate was secreted. The secretory maximum was 150 mumol . kg body wt-1 . h-1 at 5 mM plasma sulfate. DIDS inhibited sulfate secretion in vivo. In vitro sulfate uptake by renal tubule fragments was saturable (Km = 0.92 mM) and could be inhibited by DIDS, SITS, and antimycin A. Na-free medium and ouabain also inhibited sulfate uptake, suggesting involvement of the bath-to-cell Na gradient in sulfate secretion. However, no Na effect on sulfate uptake could be demonstrated in brush border membrane (BBM) or basolateral membrane (BLM) vesicles. Instead, concentrative sulfate uptake (i.e., overshoot) by BLM but not BBM vesicles could be produced by an out greater than in proton gradient. Generation of an inside-positive membrane potential (valinomycin in the presence of an out greater than in potassium gradient) slightly stimulated sulfate uptake by BLM and had no effect on BBM, indicating that the rate-limiting step for sulfate uptake at both membranes was an electroneutral process. H+ gradient-dependent sulfate uptake by BLM was inhibited by the proton ionophore FCCP, by the anion transport inhibitor DIDS, and by HgCl2. A tentative model of sulfate secretion is proposed.
Localization of the vitamin D-dependent calcium-binding protein in mammalian kidney
Authors: Roth J. , Brown D. , Norman A. W. , Orci L.
Published: December 2017

The vitamin D-dependent calcium-binding protein (CaBP) was localized by immunocytochemistry in the rat and human kidney. In both species 80% of the cells lining the distal convoluted tubules contained CaBP. In the connecting segment and the initial collecting tubule of rat kidney, 50% of the cells was positive; in the outer medullary collecting duct only 15% was positive. In the human kidney, collecting ducts in medullary rays contained 50% positive cells, whereas in the rest of the medulla no positive cells were found. The CaBP-positive cells were identified as principal or clear cells by immunoelectron-microscopy, using the protein A-gold technique. Mitochondria-rich dark cells were negative. In principal cells, CaBP immunoreactive sites were found throughout the cytosol and the nuclear euchromatin. No preferential labeling of cellular membranes was found. The data show that CaBP-positive cells are present in tubular regions that are important in regulating the final excretion of calcium. However, the subcellular distribution of CaBP does not suggest a role in the initial transmembrane transport of Ca2+ but rather indicates an involvement in processes regulating intracellular calcium.
Heterogeneity of organic base secretion by proximal tubules
Authors: McKinney T. D.
Published: December 2017

Rabbit renal tubules were perfused in vitro to characterize the secretion of the organic base procainamide by proximal tubules. When [3H]-procainamide was added to the bath it was secreted into the tubule lumen. In tubules from superficial nephrons secretory rates were greatest in S1, intermediate in S2, and lowest in S3 segments. In juxtamedullary tubules secretory rates were greatest in S1 and S2 and lowest in S3 segments. Secretory rates of p-aminohippurate were greatest in S2 and lowest in S1 and S3 segments of both superficial and juxtamedullary nephrons. The results indicate that there is both axial and internephronal heterogeneity for the secretion of this organic base by rabbit proximal tubules. The segmental secretion of procainamide differs from that of p-aminohippurate.
Prostaglandin in renin release during sodium deprivation
Authors: Francisco L. L. , Osborn J. L. , DiBona G. F.
Published: December 2017

This study was designed to examine the role of prostaglandins in the macula densa-mediated increase in plasma renin activity (PRA) during dietary sodium deprivation in rats. Micropuncture collections of early distal (ED) tubular fluid (TF) and measurements of PRA, arterial pressure (AP), and renal blood flow (RBF) were obtained in four groups of animals. Groups I and II received a normal Na diet and groups II and IV received a low Na diet; groups II and IV received indomethacin. Studies were performed after surgical denervation of the kidneys; AP and RBF were not different among the four groups of animals. EDTFna delivery was lower in groups III (0.20 +/- 0.04 neq/min) and in group IV (0.16 +/- 0.01 neq/min) animals on the low Na diet as compared with group I (0.34 +/- 0.02 neq/min) and group II (0.32 +/- 0.05 neq/min) animals on the normal Na diet. In association with the lower EDTFna delivery, the animals receiving vehicle in group III had an elevated PRA (31.46 +/- 8.81 ng/ml) as compared with group I animals on the normal Na diet receiving vehicle (4.78 +/- 1.64 ng/ml). This rise in PRA was abolished in the animals in group IV (4.06 +/- 0.81 ng/ml) that received indomethacin. We conclude that the increase in PRA, possibly resulting from macula densa receptor stimulation, during dietary Na deprivation is dependent on prostaglandin synthesis.
Effect of renal nerve stimulation on NaCl and H2O transport in Henle's loop of the rat
Authors: DiBona G. F. , Sawin L. L.
Published: December 2017

To assess the effect of renal nerve stimulation on sodium, chloride, and water transport in the loop of Henle, experiments were performed in anesthetized hydropenic and isotonic saline volume-expanded rats using renal clearance and Henle's loop microperfusion techniques (end-proximal convoluted tubule perfusion site, early distal convoluted tubule collection site). As compared with the control period values, low-frequency (less than 1.0 Hz) renal nerve stimulation decreased absolute and fractional urinary flow rate and sodium and chloride excretion without affecting mean arterial pressure, glomerular filtration rate, renal blood flow, or renal vascular resistance. In the loop of Henle, the absorptive transport of water was not affected, whereas the absorptive transport of sodium and chloride was increased in both hydropenic (Na 111 +/- 49 peq/min) and isotonic saline volume-expanded rats (Na 154 +/- 69 peq/min, Cl 180 +/- 52 peq/min) during low-frequency renal nerve stimulation. Low-frequency renal nerve stimulation decreases urinary sodium and chloride excretion via a direct effect of increasing renal tubular sodium and chloride reabsorption. In addition to the established effect of increasing proximal tubular sodium reabsorption, Henle's loop sodium and chloride absorption are also increased, supporting a physiological role for the adrenergic innervation of these structures.
Interrelated effects of aldosterone and plasma potassium on potassium excretion
Authors: Young D. B. , Paulsen A. W.
Published: December 2017

The interacting effects of aldosterone and plasma potassium concentration on steady-state renal potassium excretion were studied in two groups of chronically adrenalectomized dogs. In group I (six dogs, 22.9 kg) aldosterone was infused intravenously at 20 micrograms/day while potassium intake was changed in steps of 7-10 days duration from 10 to 30 to 100 meq/day. At the completion of each step, plasma potassium concentration, urinary potassium excretion, and other variables that potentially may affect renal function were measured. In group II (six dogs, 22.2 kg) a similar protocol was followed except that aldosterone was infused at 250 micrograms/day and the potassium intake levels were 30, 100, and 200 meq/day. Plasma potassium concentration and excretion data for the 20 micrograms/day group were: 3.22 +/- 0.26 meq/liter and 5 +/- 1 meq/day, 4.35 +/- 0.08 meq/liter and 21 +/- 2 meq/day, and 5.88 meq/liter and 82 +/- 3 meq/day at the 10, 30, and 100 meq/day intake levels, respectively. For the 250 micrograms/day group the values were: 2.72 +/- 0.18 meq/liter and 28 +/- 7 meq/day, 4.16 +/- 0.14 meq/liter and 71 +/- 8 meq/day, and 4.40 +/- 0.14 meq/liter and 172 +/- 26 meq/day at the 30, 100, and 200 meq/day intake levels. Therefore, the increase in aldosterone infusion rate shifted the relationship between plasma potassium concentration and potassium excretion to the left so that at a given level of plasma potassium a greater amount of potassium was excreted. In the normal range of plasma potassium concentration (4.00-4.40 meq/liter) the increase in aldosterone levels resulted in a four- to eightfold increase in daily potassium excretion.
Characteristics of glomerulotubular balance
Authors: Haberle D. A. , von Baeyer H.
Published: December 2017

Glomerulotubular balance (GTB) is defined as the ability of each successive segment of the proximal tubule to reabsorb a constant fraction of glomerular filtrate and solutes delivered to it. For maintenance of GTB the coupling of peritubular blood flow and intratubular fluid flow to the process of glomerular filtration seems to be of functional importance since tubular fluid reabsorption is significantly altered when either or both parameters are experimentally changed. In the case of peritubular blood flow, variations of tubular fluid reabsorption have been ascribed to variations of the mean net colloid osmotic pressure in the peritubular blood and its effects on the paracellular backleak of tubular resorbate. This relationship has, however, been clearly demonstrated only in volume expansion, when GTB is impaired. Under nondiuretic conditions, in which GTB typically occurs, the importance of the peritubular colloid osmotic pressure in control of tubular fluid reabsorption is less clear since variations of peritubular colloid osmotic pressure within a physiologic range exert only a negligible influence on tubular fluid transport. Pharmacologically induced alterations of peritubular hemodynamics or mean net colloid osmotic pressure can affect tubular fluid reabsorption without consistently altering the net interstitial pressure. In the case of intratubular flow rate, variations of tubular fluid reabsorption are comparable to changes seen with GTB. Such an interrelation is found only in tubules perfused by natural tubular fluid. In individual nephrons flow-dependent reabsorption cannot always be observed even when it appears that GTB is preserved in that kidney. Flow dependency of tubular fluid reabsorption might be attributed to some properties or constituents in tubular fluid rather than to some intrinsic characteristics of the tubular epithelium. Because flow dependence and tubular fluid transport are homogeneous along the tubule, fluid reabsorption might be controlled by a mechanism akin to a flow reactor. As yet it is not possible to explain GTB exclusively by peritubular or luminal control alone.
Sodium, bicarbonate, and chloride absorption by the proximal tubule
Authors: Rector F. C.
Published: December 2017

Proximal tubules are lined with epithelial cells that contain Na-K-ATPase in their basolateral cell membrane. The luminal cell membrane contains transport proteins that couple movement of many solutes to the active transport of sodium. The cells are connected by low-resistance junctional complexes that permit passive movement of solutes via a paracellular shunt pathway. Acidification is mediated by a Na/H antiporter localized specifically in the luminal membrane and a chloride-independent, voltage-dependent bicarbonate exit process in the basolateral membrane. The rate of acidification is controlled by the pH of the luminal and peritubular fluids. Reabsorption of NaCl from the high-chloride, low-bicarbonate fluid in the late proximal tubule is approximately 40% passive and 60% active. In proximal straight tubules the active component is entirely by simple rheogenic sodium transport, with chloride absorption driven through the paracellular shunt pathway by the lumen-negative PD. In convoluted tubules the active component is primarily neutral, with both sodium and chloride transported in approximately equivalent amounts through the cell. The mechanisms for neutral NaCl transport across the luminal membrane and for chloride exit across the basolateral membrane are unknown. A reduction in peritubular Starling forces (hydraulic and oncotic pressures) suppresses net proximal reabsorption by two mechanisms: 1) increased paracellular permeability with modest backleak of solutes (bicarbonate, glucose, amino acids) whose luminal concentration falls below their plasma level, and 2) specific inhibition of active neutral transcellular transport of NaCl by reduced peritubular protein concentration by some mechanism other than inhibition of Na-K-ATPase.
Intracellular pH, transepithelial pH gradients, and ADH-induced water channels
Authors: Parisi M. , Wietzerbin J. , Bourguet J.
Published: December 2017

Urinary bladders of frogs were exposed to a transepithelial proton and osmotic gradient (serosal pH 8.1, Tris or bicarbonate buffer; mucosal pH 5.8, unbuffered) while the alkalinization rate of the mucosal bath and the net water movement were simultaneously monitored. It was observed that 1) the mucosal alkalinization rate was dependent on serosal pH and buffer; 2) oxytocin increased the mucosal alkalinization rate only when serosal bicarbonate was employed, whereas the net water movement augmented both when serosal bicarbonate or Tris buffers were used; 3) amiloride did not modify the mucosal alkalinization rate either before or after oxytocin; 4) the increases in the mucosal alkalinization rate and in the net water movement induced by oxytocin (serosal bicarbonate) were negatively correlated. In other experiments intracellular pH (pHi) was estimated with the DMO distribution technique with the following results. 1) Oxytocin increased the pHi when either serosal bicarbonate or Tris buffers was used and even in the presence of a low mucosal pH (Tris buffer, pH 5.8). 2) Important cellular acidification was observed when CO2 was bubbled (to pH 5.8), whereas the hydrosmotic response to 8-bromo-cAMP was clearly inhibited. These results indicate that cellular alkalinization could play a pivotal role in action of ADH, show that ADH can modify the transepithelial pH equilibrium mechanism, and suggest that intracellular pH regulation and water permeability control can be linked regulatory processe.
Renal nerves in the pathogenesis of hypertension in experimental animals and humans
Authors: Katholi R. E.
Published: December 2017

Efferent renal innervation is composed of postganglionic sympathetic fibers to the renal arterioles, juxtaglomerular apparatus, and renal tubules. Increased efferent renal sympathetic nerve activity results in increased renal vascular resistance, renin release, and sodium retention. These responses from enhanced renal sympathetic activity contribute to normal cardiovascular homeostasis but could also facilitate the development of hypertension by shifting the arterial pressure-renal sodium excretion curve to the right. Accordingly, interruption of the renal nerves should prevent the development of hypertension in animal models in which increased sympathetic nervous system activity has been implicated. Renal denervation delays the development of hypertension and results in greater sodium excretion in the Okamoto and New Zealand spontaneously hypertensive rat and in the DOCA-salt-treated rat, suggesting that these responses are due, at least in part, to loss of efferent renal nerve activity. Similar sympathetically mediated renal vasoconstriction has been implicated in the pathogenesis of early essential hypertension in man. Recent studies indicate that the kidney is a sensory organ with mechano-receptive and chemoreceptive afferent renal nerves involved in renorenal and cardiovascular regulation. Renal denervation in established one-kidney one-clip and two-kidney one-clip Goldblatt hypertension in the rat and chronic coarctation in the dog results in an attenuation of the hypertension. The depressor effect of renal denervation in these models is not due to change in renin activity or sodium excretion but is associated with decreased activity of the sympathetic nervous system. These findings suggest that the afferent renal nerves contribute to the pathogenesis of renovascular hypertension by enhancing the activity of the sympathetic nervous system. The role of the afferent renal nerves in renovascular hypertension in humans warrants further study.
Developmental pattern of water and electrolyte transport in rat superficial nephrons
Authors: Lelievre-Pegorier M. , Merlet-Benichou C. , Roinel N. , de Rouffignac C.
Published: December 2017

Micropuncture samples were collected from late proximal and early distal sites of the same nephron in nondiuretic young rats aged 13-15, 19-21, and 30-39 days. Plasma ultrafiltrate (UF), tubular fluid (TF), and final urine were analyzed for Cl, Na, K, Mg, P, and Ca concentrations by electron probe. Between days 13 and 39, the proximal convoluted tubule reabsorbed a constant fraction of continuously increasing filtered loads of water, sodium, and potassium. The mean TF/UF concentration ratio for Cl in the late proximal tubule was 0.98 +/- 0.03 in the 13- to 15-day age group and increased to 1.20 +/- 0.03 in the 30- to 39-day age group. The mean TF/UF concentration ratio for Mg increased from 1.17 +/- 0.07 at 13-15 days to 2.07 +/- 0.22 at 30-39 days. The mean TF/UF concentration ratio for Ca at the end of the proximal tubule was found to be significantly lower than unity in the two youngest groups and higher in the oldest. Evidence was also found for maturation of the loop of Henle. The amounts of Cl, Na, K, and Ca reabsorbed by the loop, expressed in percent of the amount delivered, rose significantly with age. In contrast, mean Mg fractional reabsorption was already maximal in the youngest group. Phosphate reabsorption in the loop was limited in all three groups. It is concluded that in the 13- to 15-day rats 1) the fraction of the Na, K, and H2O filtered loads reabsorbed along the proximal tubule is already the same as in adult animals; 2) the proximal tubule epithelium is not able to create or maintain a transepithelial concentration gradient for Cl; and 3) the fractional reabsorption of Mg is higher than in the adult animal. It is also concluded that Cl, Na, K, and Ca transport along the loop of Henle all have the same maturation pattern but that the pattern for Mg is different.