bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute unilateral renal denervation in rats with extracellular volume expansion
Authors: Bello-Reuss E. , Pastoriza-Munoz E. , Colindres R. E.
Published: December 2017

Sodium reabsorption along the nephron was studied before and after acute unilateral denervation of the left kidney in anesthetized rats with extracellular volume expansion. Studies were also performed before and after sham denervation. Denervation increased urine volume (V) from the left kidney from 35.2 to 59.2 mul min-1 (P less than 0.001) and urinary sodium excretion (UNaV) from 6.9 to 11.8 mueq min-1 (P less than 0.001). The control right kidney showed a simultaneous 45% decrease in V and UNaV. Inulin clearance (GFR) and renal plasma flow (RPF) remained unchanged after denervation in both kidneys. Left kidney late proximal (F/P)m decreased from 1.50 to 1.24 (P less than 0.01); single-nephron GFR (SNGFR) remained unchanged. (F/P)m ratios were also decreased in early distal (3.87–2.65, P less than 0.005) and late distal (5.48–3.83, P less than 0.02) convolutions. Fractional and absolute Na reabsorption in the distal convolution did not decrease. GFR, RPF, V, UNa, late proximal (F/P)m, and SNGFR were unchanged in shamdenervated rats. The increases in V and UNa V produced by acute renal denervation in the volume-expanded anesthetized animal are thus caused by further depression of proximal tubular salt and water reabsorption.
Lost mass and excretion as stimuli to parabiotic compensatory renal hypertrophy
Authors: Obertop H. , Malt R. A.
Published: December 2017

To help determine the roles of lost renal mass and lost excretory ability in producing renoprival hypertrophy, observations were made in otherwise normal rats cross-circulated for 24 h with rats prepared in one of the following ways: bilateral nephrectomy, bilateral ureteral ligation, or bilateral nephrectomy with 24 h of uremia. Bilateral nephrectomy produced parabiotic increases in renal mass and in the average cellular concentration of RNA: bilateral ureteral ligation did not. Uremia did not potentiate the effects of bilateral nephrectomy. Lost mass is the determinant of compensatory renal hypertrophy.
A signal-processing system for real-time ultrasonic measurement of urine flow parameters
Authors: Albright R. J. , Peterson J. R.
Published: December 2017

An application of a signal-processing system to the urethra is described which allows for real-time measurement of the average velocity of the urine at a particular location along the urethra during voiding through measurement of the average frequency in ultrasonic return from scatterers in the flowing urine. In addition, this comparatively simple system provides, without additional instrumentation, the relative urethral cross-sectional area at this location and the relative urine flow rate as functions of time throughout the voiding period. Tests indicate its potential as a valuable transcutaneous diagnostic aid in the detection, study, and treatment of various disorders and diseases of the lower urinary system. The key element of the system is a circuit having a voltage transfer function magnitude proportional to the square root frequency.
Renal handling of the polar DDT metabolite DDA (2,2-bis[p-chlorophenyl] acetic acid) by marine fish
Authors: Pritchard J. B. , Karnaky K. J. , Guarino A. M. , Kinter W. B.
Published: December 2017

The renal handling of 2,2-bis(p-chlorophenyl) acetic acid (DDA) was examined in the isolated tubules of the winter flounder (Pseudopleuronectes americanus) in vitro in conjunction with clearance studies in the flounder and in the aglomerular goosefish (Lophius americanus). In vitro, both uptake studies and autoradiography showed extensive energy-dependent accumulation within the cytoplasm of tubular cells and the tubular lumen. The uptake was strongly inhibited by p-aminohippurate and chlorophenol red. A second component of uptake was insensitive to metabolic inhibitors or organic acids and represented tissue binding. In vivo, both species showed net secretion which was inhibited by probenecid. Comparison of DDT and DDA distribution and excretion emphasized the importance of the greater water solubility of DDA and of its secretory transport, since DDA was excreted at over 200 times the rate of DDT. Liver, kidney, and bile also showed elevated DDA tissue-to-plasma ratios. Thus, the organic acid system mediates the accumulation and excretion of DDA in these fish.
Techniques for microdrop analysis of fluids (sweat, saliva, urine) with an energy-dispersive X-ray spectrometer on a scanning electron microscope
Authors: Quinton P. M.
Published: December 2017

Volumes of 10(-10) liter of sweat, saliva, and urine were analyzed with an energy-dispersive spectrometer (EDS) X-ray analyzer on a standard scanning electron microscope (SEM). Results of the EDS analysis of diluted and undiluted samples were verified by comparison with results of analyses of the same sample prepared by conventional quantitative methods. Except for Cl in concentrated urines and Mg in low concentrations, good agreement was found between the methods. The analysis provides quantitation of most elements of biological interest present in concentrations of about 1 mM, while it demonstrates good linearity (r greater than 0.99) throughout a wide range of commonly encountered biological concentrations. Reproducibility of the analysis is on the order of 2% and the minimal determinable concentration is generally between 0.5 and 1.0 mM for S, P, K, and Ca and slightly more than 1.0 mM for Mg.
Influence of steady-state PaCO2 on escape from ADH-induced water retention in the dog
Authors: Kaehny W. D. , Gougoux A. , Cohen J. J.
Published: December 2017

The influence of the prevailing PaCO2 on the water-retaining effects of sustained elevations in ADH was assessed by administering vasopressin (5 U in oil, twice daily) and a fixed water intake to dogs with eucapnia (n, 7), chronic hypercapnia (n, 6), and chronic hypocapnia (n, 8). Although water excretion initially fell to a similar extent in all three groups, cumulative water retention by day 4 of vasopressin administration was 77 mg/kg in the hypocapnic group, 46 ml/kg in the eucapnic group, and only 14 ml/kg in the hypercapnic group. These differences were reflected in a marked disparity in the degree of hyposmolality of body fluids, plasma osmolality falling by day 4 to an average value of 223, 237, and 268 mosmol/kg in the hypocapnic, eucapnic, and hypercapnic animals, respectively. In a separate group of dogs, water deprivation and water loading studies revealed that sustained hypercapnia does not affect the maximal concentrating or diluting ability of the kidney. We conclude, therefore, that the striking influence of the prevailing PaCO2 on the water-retaining effects of administered vasopressin cannot be ascribed to an altered responsiveness of the nephron per se, but that this influence reflects an alteration in the ease with which the kidney can escape from the antidiuretic effects of this substance.
Renal autoregulation: perspectives from whole kidney and single nephron studies
Authors: Navar L. G.
Published: December 2017

The phenomenon of renal autoregulation is often thought to relate only to the manner in which the kidney responds to changes in arterial pressure. This review presents a more comprehensive description of the process based on the intrinsic renal vascular responses to changes in arterial pressure, venous pressure, ureteral pressure, and plasma colloid osmotic pressure. Regulation of glomerular filtration rate (GFR), or some function thereof, is the feature most consistently observed. More specifically, in response to external manipulations that change GFR, autonomous changes in renal vascular resistance tend to return GFR back towards normal. The bulk of the evidence suggests that the requisite renal vascular resistance alterations occur predominately at preglomerular segments. Most of the whole kidney autoregulatory responses can be explained on the basis of the distal tubule-glomerular feedback hypothesis, thought to be mediated by the macula densa-juxtaglomerular complex, which states that increases in distal volume delivery lead to increases in afferent arteriolar resistance while reduced distal delivery leads to afferent arteriolar dilation. Micropuncture data have demonstrated that interruption of distal volume delivery prevents single nephrons from autoregulating GFR and glomerular pressure. Also, single nephron glomerular filtration rate (SNGFR) based on proximal collections is higher than SNGFR measured by distal collections or with an indicator-dilution technique. Studies utilized direct microperfusion of the distal nephron from a late proximal tubule site have demonstrated that SNGFR and glomerular pressure decrease in response to increases in distal nephron perfusion rate. Although experiments in rats have been interpreted as indicating that distal chloride concentration and/or reabsorption most likely mediate the feedback responses, recent studies in dogs have demonstrated that feedback responses can be consistently obtained with nonelectrolyte perfusion solutions. These latter studies suggest that the feedback response may be sensitive to some function of total solute delivery or concentration. At present, there is no clear understanding of the intracellular events that link the compositional alterations occurring within the early distal tubule to the final effector system.
Influence of parathyroid hormone on glomerular ultrafiltration in the rat
Authors: Ichikawa I. , Humes H. D. , Dousa T. P. , Brenner B. M.
Published: December 2017

Experiments were performed on 22 plasma-expanded Munich-Wistar rats to investigated the effects of parathyroid hormone (PTH) on the determinants of glomerular ultrafiltration. Mean values for single nephron filtration rate (SNGFR), glomerular plasma flow rate (QA), systemic oncotic pressure, and transglomerular hydraulic pressure difference (deltaP) were similar in acutely thyroparathyroidectomized (TPTX) rats and non-TPTX rats. Nevertheless, the glomerular capillary ultrafiltration coefficient (Kf) was uniformly higher in TPTX rats (greater than 0.113 +/- 0.005 (SE) nl/(s.mmHg)] than in non-TPTX controls (0.088 +/- 0.005). In TPTX rats, infusion of a submaximal dose (1 U/kg per min) of PTH resulted in significant decreases in SNGFR at constant QA and deltaP, due primarily to return of Kf to non-TPTX levels. Infusion of 10 U/kg per min of PTH to non-TPTX rats further reduced Kf, on average to 0.042 +/- 0.001 nl/(s.mmHg), leading to further reduction in SNGFR, whereas QA and deltaP again remained constant. These findings suggest that PTH may play an important role in modulating Kf, and consequently, SNGFR.
Potassium reabsorption and secretion in the perfused bullfrog kidney
Authors: Deeds D. G. , Sullivan L. P. , Welling D. J.
Published: December 2017

Techniques have been developed for obtaining comparative estimates of the rates of K secretion and reabsorption in the artificially perfused bullfrog kidney and the use of 42K infused into the portal circulation. In control experiments in which Kexc/Kfilt averaged 0.65, approximately 30% of filtered K escaped reabsorption and excreted K was composed of roughly equal parts of filtered K and secreted K. Fractional reabsorption of K was constant at 70% over a wide range of filtration rates. The rate of K secretion correlated significantly with the rate of Na reabsorption and with the urine flow rate. Acetazolamide stimulated secretion and inhibited reabsorption.
Ammonia metabolism
Authors: Tannen R. L.
Published: December 2017

The pathways responsible for an the mechanisms underlying the adaptive increase in ammonia production in response to acidosis are considered. It seems unlikely that the cytosolic pathways (glutamine synthetase, glutaminase II, phosphate-independent glutaminase, and gamma-glutamyl transferase) are of primary importance in the adaptive process, but the role of the purine nucleotide cycle has not been resolved. The intramitochondrially located phosphate-dependent glutaminase pathway is generally believed to be of primary importance. Adaptation involved either enhanced glutamine entry into the mitrochondria and/or activation of phosphate-dependent glutaminase, but the relative importance of each has not been resolved definitively. The overall adaptive response is probably modulated by factors regulating alpha-ketoglutarate metabolism to phosphoenolpyruvate, and possibly also by metabolism of TCA cycle intermediates. It seems unlikely that a decrease in systemic pH is the direct effector for the acidosis-induced increase in ammonia formation; however, the resulting decrease in urine pH may play a critical role. Other potential messengers, including potassium, glucocorticoids, mineralocorticoids, cyclic AMP, and calcium probably do not serve a primary function, but the importance of other circulating factor(s) is unclear.
Renal potassium transport: contributions of individual nephron segments and populations
Authors: Wright F. S. , Giebisch G.
Published: December 2017

General features of the processes that contribute to renal potassium excretion are understood from clearance, stop-flow, micropuncture, and in vitro microperfusion experiments. However, the complex architecture of the kidney has made it difficult to examine individual nephron segments in all parts of the kidney. Accordingly, the extent to which distinguishable nephron populations, such as superficial and deep, may differ in their contributions to overall potassium excretion are not known. Also, the nature of transport processes across the successive segments of the nephrons (including not only the underlying cellular mechanisms, but even the direction of transport) is not known for all segments in any one nephron population. Excreted potassium is derived both from filtered potassium that escapes reabsorption and from secreted potassium. The filtered portion is large in amphibians and may be larger than generally recognized in mammals. The remainder is secreted primarily by distal nephron segments (distal tubule and cortical collecting duct). Potassium is also secreted into descending limbs of Henle loops; apparently this fraction is recycled from collecting ducts, and so does not represent an additional quantity of potassium transferred from blood to tubule fluid. Systemic factors that affect potassium excretion (potassium intake, sodium chloride intake, mineralocorticoid hormone levels, acid-base balance, and diuretic treatments) do so by modifying the net uptake of potassium from blood to cell and by altering the rate of fluid flow through the distal nephron. Under most circumstances, the distal nephron in the cortex appears to secrete potassium and the medullary collecting duct reabsorbs potassium. Although it is clear that successive nephron segments transport potassium in different ways, evidence to date does not indicate that potassium is handled differently by superficial nephrons compared to nephrons whose glomeruli lie in the deeper levels of the cortex.
Effect of decreased renal sympathetic nerve activity on renal tubular sodium reabsorption
Authors: Prosnitz E. H. , DiBona G. F.
Published: December 2017

The effect of decreases in renal sympathetic nerve activity on renal tubular sodium reabsorption was examined in anesthetized dogs. Reflex decreases in renal sympathetic nerve activity were produced by left atrial distention and stellate ganglion stimulation. Both interventions produced significant decreases in directly recorded efferent renal sympathetic nerve activity of 42 and 36%, respectively. With renal perfusion pressure held constant, neither glomerular filtration rate nor renal blood flow were significantly altered, but significant and reversible increases in urine flow and sodium excretion occurred. These studies demonstrate that reflex decreases in efferent renal sympathetic nerve activity result in decreases in renal tubular sodium reabsorption without changes in renal hemodynamics.
Relationship between PAH transport and Na-K-ATPase activity in the rabbit kidney
Authors: Spencer A. M. , Sack J. , Hong S. K.
Published: December 2017

The relationship between Na-K-ATPase activity and p-aminohippurate (PAH) transport was examined in renal cortical slices of mixed-breed rabbits by using ouabain to vary the level of Na-K-ATPase activity. Ouabain increased passive PAH uptake, measured in the presence of probenecid. Slice homogenate Na-K-ATPase activity was inhibited by 50% with about 2 X 10(-6) M ouabain. When the concentration was 10(-5) M or above, active PAH uptake was inhibited. Lower concentrations (10(-7) and 10(-6) M) of ouabain stimulated active PAH uptake. Acetate stimulated PAH uptake when medium ouabain was less than 10(-4) M. Ouabain, 10(-5) M and higher, caused intracellular K+ to fall and Na+ to rise. The changes in active PAH uptake observed with ouabain correlated much better with changes in intracellular K+ or Na+ levels (P less than 0.01) than with changes in slice homogenate Na-K-ATPase activity. Vmax for active PAH uptake decreased with 5 X 10(-5) M ouabain, and tended to increase with 10(-7) M ouabain. Ouabain did not alter Km for active PAH uptake. The data support the hypothesis that there is a functional link between active PAH transport and Na-K-ATPase activity. This linkage may be an indirect one mediated by changes in intracellular cation concentrations.
Effects of ouabain on potassium transport in the perfused bullfrog kidney
Authors: Wilkinson H. L. , Deeds D. G. , Sullivan L. P. , Welling D. J.
Published: December 2017

We studied the effect of ouabain on transepithelial and cellular potassium transport in the isolated perfused bullfrog kidney. We used recently developed techniques for estimating the unidirectional reabsorptive and secretory K fluxes (Jr and Js) and measuring the kinetics of cellular K transport. Two hours of perfusion with 1 X 10(-6) M ouabain did not affect GFR, reduced fractional Na reabsorption 57%, increased K excretion 41%, and inhibited Jr 34%. Js rose 68% at 60 min and then returned to the control level. Ninety minutes of perfusion with 5 X 10(-6) M ouabain reduced GFR 28% and fractional Na reabsorption 76%. K excretion rapidly increased 71% within 30 min and then fell to 60% of the control level, while Jr fell 64%. Js rose 42% in 30 min and then fell to 23% of the control level. Both doses reduced K uptake into cellular pools from the circulation and increased the rate coefficients for efflux into tubular fluid. The data indicate that ouabain inhibited reabsorption and transiently accelerated the rate of loss of K from the cells into the tubular fluid. This initially masked the ultimate inhibition of K secretion from the circulation into the tubular fluid.
Effect of acute ureteral obstruction on terminal collecting duct function in the weanling rat
Authors: Buerkert J. , Martin D. , Head M.
Published: December 2017

Micropuncture techniques were employed to evaluate the effects of unilateral ureteral obstruction (UUO) of 18 h duration on the function of the terminal collecting duct in weanling rats 90-120 min following release of obstruction. In control animals and after release of UUO, water and sodium reabsorption continued along the terminal segment of the collecting duct. Fractional delivery of water (FRH2O) and sodium (FRNa) to this segment was increased after release of UUO. A significantly greater amount of the FRH2O and FRNa was reabsorbed along the terminal collecting duct following release of obstruction than in controls. Potassium was not consistently reabsorbed or secreted in either group. Following release of UUO, the osmolality of collecting duct fluid was lower than in controls, but was not different from the osmolality of fluid obtained from the bend of the loop of Henle. The results suggest that the permeability to water and the reabsorptive capacity of the collecting duct are not altered by acute obstruction.
Ionic requirements of proximal tubular sodium transport. III. Selective luminal anion substitution
Authors: Green R. , Bishop J. H. , Giebisch G.
Published: December 2017

The effect of substitution of luminal anions on sodium and fluid absorption in rat renal proximal convoluted tubules was studied with continuous luminal microperfusion methods. Substitution of bicarbonate in the control Ringer perfusion fluid by 25 mM acetate reduced net sodium reabsorption by 40%; substitution by chloride reduced it by 25%; and substitution by cyclamate reduced it by 70%. Infusion of acetazolamide reduced net sodium and fluid transport in all cases except chloride-Ringer perfusion. Cyanide added to the perfusion fluid inhibited fluid and sodium movement completely when there was no imposed chloride concentration gradient, but only reduced fluid and solute movement by 68% when a nominal 36 mM transepithelial chloride concentration gradient existed. We conclude from these observations that passive forces for sodium reabsorption can account for a moderate amount of sodium transport, that the effects of acetazolamide in low concentrations are dependent on the presence of bicarbonate in the lumen, and that some anions alter net sodium transport either by reducing the availability of permeant anion for co-transport with sodium or by a direct effect on the sodium and/or chloride transport systems.
Effects of parathyroid hormone on electrolyte transport in the hamster nephron
Authors: Harris C. A. , Burnatowska M. A. , Seely J. F. , Sutton R. A. , Quamme G. A. , Dirks J. H.
Published: December 2017

Recollection micropuncture and clearance studies were carried out on thyroparathyroidectomized hamsters to clarify the localization of the effects of parathyroid hormone (PTH) on renal electrolyte transport. The clearance data confirmed that PTH inhibits phosphate and enhances calcium and magnesium reabsorption. These effects appeared to result from actions of the hormone in several parts of the nephron. In the proximal tubule PTH did not affect H2O reabsorption but inhibited phosphate reabsorption ((TF/P)PO4 increased from 0.46 +/- 0.04 to 0.57 +/- 0.03, P less than 0.02) and appeared to enhance calcium and magnesium reabsorption ((TF/UF)Ca decreased from 1.41 +/- 0.07 to 1.25 +/- 0.06, P less than 0.001, and (TF/UF)Mg from 1.66 +/- 0.10 to 1.51 +/- 0.08, P less than 0.05; in control animals (TF/UF)Ca increased from 1.51 +/- 0.10 to 1.65 +/- 0.11, P less than 0.01). PTH further inhibited phosphate reabsorption and enhanced calcium and magnesium reabsorption between the late proximal and early distal sites of puncture. Comparison of fractional deliveries of calcium and magnesium from the late distal tubule with their fractional excretions suggests an additional effect beyond the distal puncture site. The phosphaturic, but not the calcium- and magnesium-retaining, effects of PTH were abolished by a 16-h fast.
Peritubular capillary control of proximal tubule reabsorption in the rat
Authors: Quinn M. D. , Marsh D. J.
Published: December 2017

Changes in peritubular capillary hydrostatic and oncotic pressures, which probably affect net interstitial pressure and, thus, the force on fluid movement across the tubule basement membrane, can modulate absolute proximal reabsorption rate (APR). To examine the relationship between APR and net interstitial pressure, we measured peritubular capillary hydrostatic and oncotic pressure, single nephron filtration rate, APR, absolute distal reabsorption (ADR), and tubular hydrostatic pressure in hydropenic, saline-loaded, and plasma-loaded rats. Net interstitial pressure in saline loading was estimated from subcapsular hydrostatic pressure and lymph protein concentration measurements. The surface area-hydraulic conductivity product of the peritubular capillary network was estimated from these measurements with a model of capillary fluid exchange in which fluid uptake was defined to be APR plus ADR. The estimated value was assumed to remain constant in all three states, and was then used to estimate net interstitial pressure in hydropenic and plasma-loaded rats. APR and net interstitial pressure correlated strongly, a finding consistent with the hypothesized role for net interstitial pressure in regulating proximal reabsorption.
Renal prostaglandin E2 secretion and excretion in conscious dogs
Authors: Zambraski E. J. , Dunn M. J.
Published: December 2017

Renal prostaglandin E2 (PGE2) secretion and excretion rates were determined in nine conscious dogs. Renal venous (RV) and urine PGE2 concentrations were measured by radioimmunoassay. In 21 controls tests RV PGE2 ranged from 37 to 215 pg/ml, with a mean concentration of 97 +/- 11 pg/ml. Basal left kidney PGE2 secretion was 317 +/- 42 pg.g-1.mm-1. Urine PGE2 concentration averaged 8,320 +/- 1,510 pg/ml with a PGE2 excretion rate of 3,260 +/- 480 pg/min from both kidneys. Indomethacin (2 mg/kg) reduced RV and urine PGE2 concentrations by 60 and 77%, respectively. Meclofenamate (2 mg/kg) decreased RV and urine PGE2 concentrations by 36 and 48%, respectively. PG inhibition had no significant influence on blood pressure or renal blood flow (RBF). PG inhibition reduced urine flow rate and increased urine osmolality. Indomethacin had no effect on urine sodium concentration or sodium excretion; meclofenamate increased urine sodium concentration and slightly diminished sodium excretion. These data demonstrate that PGE2 is released from the kidney in a conscious animal and that both indomethacin and meclofenamate significantly reduce the renal secretion and excretion of PGE2. In a normal, conscious animal prostaglandins do not control blood pressure or RBF but are involved in the excretion of water.
Effect of volume expansion on renal glucose transport in normal and uremic dogs
Authors: Wen S. F. , Stoll R. W.
Published: December 2017

Proximal and distal tubule micropuncture studies were performed in normal and uremic remnant-kidney dogs to examine the tubule mechanism of glucose reabsorption before and after 10% extracellular volume expansion. In normal dogs volume expansion markedly inhibited glucose reabsorption in the proximal convoluted tubule, but the ensuing increase in further distal glucose delivery was nearly completely reabsorbed in the intermediate segment (between late proximal tubule and distal tubule). In the uremic, remnant-kidney dogs, glomerulotubular balance for glucose was well maintained in the proximal convoluted tubule despite an adaptive increase in nephron filtration rate. Volume expansion markedly increased glucose delivery out of the proximal convoluted tubule and an incomplete glucose reabsorption in the intermediate segment led to glycosuria. When glucose delivery to the intermediate segment was increased to a comparable degree by subthreshold glucose loading in hydropenic normal dogs, glucose reabsorption in this segment was virtually complete, suggesting that in the volume-expanded uremic dogs glucose reabsorptive capacity in the intermediate segment was reduced. Thus, the intermediate segment appears to play a significant role in the fine regulation of urinary glucose excretion.
Effect of fluoroacetate on the inhibitory action of ketone bodies and fatty acids on renal ammoniagenesis
Authors: Lemieux G. , Baverel G. , Vinay P. , Gougoux A.
Published: December 2017

Renal cortical slices from acidotic dogs (NH4CL) were incubated at pH 7.0 with L-glutamine (1 and 5 mM) or L-glutamate (5 mM) with or without DL-beta-hydroxyburyrate 1 mM, acetoacetate 0.5 mM, as well as oleate, palmitate, octanoate, and crotonate 0.5 mM and in the presence or absence of fluoroacetate 0.05 mM. Fluoroacetate alone increased glutamine or glutamate uptake and ammoniagenesis whereas gluconeogenesis rose only when glutamine 5 mM or glutamate were used. Alanine production also rose by 30% when glutamine but not glutamate was used as substrate in the presence of fluoroacetate. Efficient blocking of the Krebs cycle at the aconitase level by fluoroacetate was evidenced by the release of citrate in the incubation medium and by a slight but significant decrease in oxygen consumption (10-20%). The marked decrease in glutamine uptake, ammoniagenesis, and gluconeogenesis induced by ketone bodies and fatty acids was completely corrected by addition of fluoroacetate. The present studies demonstrate that ketone bodies and fatty acids inhibit renal ammoniagenesis and gluconeogenesis in vitro through their oxidation in the mitochondria. They also suggest that direct transamination of glutamine into alanine (glutaminase II pathway) may be significant when oxidation of pyruvate is inhibited by fluoroacetate.
Transport and metabolism of octanoate by the perfused rat kidney
Authors: Trimble M. E.
Published: December 2017

These studies were done to determine the capacity of the perfused rat kidney to metabolize and transport the medium-chain fatty acid, octanoate (C8). Use of C8, which is water soluble, facilitated the study of transport, since protein, normally needed to transport long-chain fatty acids in solution, could be omitted from the perfusate. Using a filtering kidney it was found that total metabolism and incorporation of [1-14C]octanoate occurred at a rate of 3.9 +/- 0.3 micromol-g wet wt-1-20 min-1 when the perfusate octanoate was 2.8 mM, and reabsorptive uptake occurred at the rate of 7.5 +/- 1.3 micromol-g wet wt-1-20 min-1 at the same octanoate concentration. Use of a nonfiltering kidney (10% dextran perfusate) allowed quantitation of peritubular octanoate uptake. This peritubular uptake showed saturation above 0.7 mM perfusate octanoate with an apparent transport maximum (Tmax) at 2.1 micromol-g wet wt-1-20 min-1. Many previous experiments have linked renal fatty acid transport with that of the organic anion transport system. The apparent peritubular Tmax observed for octanoate suggests carrier-mediated transport. However, this transport did not appear to be inhibited by other organic acids such as probenecid (1--2 mM) and p-aminohippurate (1--2 mM).
Physiological basis for absorptive and renal hypercalciurias
Authors: Pak C. Y.
Published: December 2017

Idiopathic hypercalciuria constitutes two major variants-absorptive hypercalciuria, characterized by a primary intestinal hyperabsorption of calcium, and renal hypercalciuria, in which renal tubular reabsorption of calcium is primarily impaired. The two forms of hypercalciuria may be distinguished from each other, since a) parathyroid function is stimualted in renal hypercalciuria, but normal or suppressed in absorptive hypercalciuria, b) the renal leak of calcium is present in renal hypercalciuria, but not in absorptive hypercalciuria, c) intestinal calcium absorption is probably increased primarily in absorptive hypercalciuria, and secondarily in renal hypercalciuria (from parathyroid hormone excess), d) the increased calcium absorption in renal hypercalciuria probably results from the parathyroid hormone-dependent stimulation of 1,25–dihydroxyvitamin D synthesis, whereas that in absorptive hypercalciuria may be vitamin D-independent, e) the response of the two conditions to certain treatments is unique, and f) the sequelae of parathyroid hormone excess, such as low bone density and negative calcium balance, may be present in renal hypercalciuria, but not in absorptive hypercalciuria. These findings provide a physiological basis for the consideration of absorptive and renal hypercalciurias as distinct and separate entities.
Dissociative effects of piretanide on proximal tubular PO4 and HCO3 transport
Authors: Winaver J. , Sylk D. B. , Teredesai P. R. , Robertson J. S. , Puschett J. B.
Published: December 2017

The effect of piretanide on renal electrolyte transport was evaluated by simultaneous micropuncture and clearance studies. In chronically thyroparathyroidectomized (TPTX) dogs, the drug caused an increased percentage excretion (%E) of sodium (from 0.6 +/- 0.1 to 15.2 +/= 1.8%, P less than 0.01) as well as of calcium (from 1.0 +/- 0.2 to 17.8 +/- 1.7%, P less than 0.001) and bicarbonate (from 1.2 +/- 0.4 to 5.9 +/- 0.9, P less than 0.001), but there was no change in %E of phosphate (4.0 +/- 0.9 to 6.6 +/- 1.6, P less than 0.10). In the presence of a constant infusion of parathyroid hormone (PTH) the drug caused a greater degree of natriuresis, calciuria, and bicarbonaturia and a significant increase in %E of PO4 (from 7.4 +/- 1.6 to 20.0 +/- 2.1, P less than 0.05). Proximal fractional reabsorption (PFR) of PO4 was unaffected, but there was a significant decrease in PFR of sodium, calcium, and bicarbonate in the TPTX dogs. The presence of PTH did not alter the effects of piretanide on PFR of phosphate and bicarbonate. There was no change in urinary or tubular fluid pH in either group of dogs. These data indicate that piretanide dissociates proximal PO4 transport from that of sodium and bicarbonate. In the presence of PTH, the drug inhibits PO4 transport beyond the late proximal convoluted tubule. In addition, tubular (and urinary) pH appears to be an important regulator of PO4 transport, especially in the absence of PTH.
Renal potassium adaptation: Na-K-ATPase activity along the nephron after chronic potassium loading
Authors: Doucet A. , Katz A. I.
Published: December 2017

To identify nephron sites where renal potassium adaptation takes place, Na-K-ATPase was measured with a micromethod along the nephron of potassium-loaded mice. A possible role of aldosterone in this process was evaluated in K-loaded animals treated concurrently with pharmacologic doses of spironolactone. Animals fed a potassium-enriched diet for at least 2 wk excreted about 90% of ingested potassium in the urine, and fractional potassium clearance averaged 87 +/- 8%, compared with 13 +/- 2% in controls. Na-K-ATPase activity per millimeter tubule length increased by 225% in the cortical collecting tubule and by 177% in the medullary collecting tubule, but was not substantially affected in other nephron segments. Stimulation of Na-K-ATPase was identical in the cortical collecting tubule of K-loaded mice treated with spironolactone. These results indicate that chronic potassium loading in the mouse results in an adaptive increase potassium loading in the mouse results in an adaptive increase in Na-K-ATPase in the collecting tubule and suggest that this nephron segment is the major site of potassium adaptation in this species. This effect appears to be independent of aldosterone.
Anatomy of the juxtaglomerular apparatus
Authors: Barajas Luciano
Published: December 2017

Page F333: Luciano Barajas. “Anatomy of the juxtaglomerular apparatus.” Page F338: left column, lines 6–8 should read: Their work, for example, was carried out on renal tissue fixed by immersion in formaldehyde followed by osmication of the blocks.
Abnormalities of cell volume regulation and their functional consequences
Authors: Pollock A. S. , Arieff A. I.
Published: December 2017

Disturbances of body fluid osmolality are common as clinical entities. The primary clinical manifestations of both hyper- and hyposmolal states are central nervous system dysfunction. With hyperosmolal perturbations in plasma osmolality, the brain, like other tissues, initially acts as a "perfect osmometer," passively shrinking as a result of secondary substantial cellular water loss. In hours to days, depending on the extracellular solute, restoration of brain volume may be achieved if the solute is endogenous (Na+, urea, glucose). This occurs largely by the generation of new, nonelectrolyte intracellular solute in brain. This de novo solute appears only when hyperosmolality is caused by endogenous substances and not with mannitol, glycerol, or radiographic contrast media. Under the latter circumstances, the brain remains dehydrated and idiogenic osmoles are not observed. In hyposmolal states, the brain initially acts as an "imperfect osmometer," expanding its volume less than expected on the basis of passive water movement. Other tissues (red cell, muscle, and liver) behave more as perfect osmometers. In time, restoration of cell volume is achieved largely through loss of intracellular electrolytes (Na+ and K+) and other solutes such as amino acids. Teleologically, these mechanisms appear to protect brain volume at the expense of the intracellular milieu. The resultant alteration of intracellular composition may be largely responsible for the diffuse alterations in brain function observable in patients and experimental animals with such afflictions.
Luminal influences on potassium secretion: transepithelial voltage
Authors: Good D. W. , Wright F. S.
Published: December 2017

In vivo microperfusion techniques were used to evaluate whether changes in luminal fluid flow rate affect late distal tubule transepithelial voltage (VTE) and to determine whether flow-dependent changes in K secretion by the renal distal tubule of the rat that we observed previously could be attributed to changes in electrical driving forces. Results showed that increasing the perfusion rate from 6 to 26 nl/min of solutions containing either 94, 46, or 15 mM sodium and 2 mM potassium caused VTE to become 10-12 mV less lumen negative. Since increasing perfusion rate decreases VTE, a flow-dependent voltage change is not responsible for the effect of increasing luminal flow rate to increase distal K secretion. To evaluate the possible contribution of changes in luminal Na and K concentrations to the flow-dependent changes in VTE, the effects of changing either Na or K concentration at constant flow rate were examined. These studies showed that 1) changes in luminal Na concentration within the physiological range (44-94 mM) have no detectable effect on VTE; 2) increases in luminal K concentration within the physiological range (5-16 mM) significantly increase VTE; and 3) the flow-dependent depolarization of VTE is primarily caused by flow-dependent changes in luminal K concentration.
Covalent modification and inhibition of an epithelial sodium channel by tyrosine-reactive reagents
Authors: Park C. S. , Fanestil D. D.
Published: December 2017

This study sought to elucidate the molecular mechanism involved in the Na+ entry across the apical membrane of the urinary bladder of the toad. Na+ transport, as measured by short-circuit current (SCC), was irreversibly inhibited by three tyrosine-specific reagents: N-acetylimidazole (ID50, 4.6 x 10(-2)M), tetranitromethane (1.8 x 10(-4) M), and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl; 3.4 x 10(-5) M). The functional specificity of NBD-Cl to block Na+ entry via Na+ channels was attested by the following: 1) NBD-Cl produced comparable inhibition of SCC and Na+ influx under aerobic and anaerobic conditions; 2) amphotericin B produced complete recovery of inhibited SCC; 3) vasopressin increased SCC only in proportion to the uninhibited SCC; 4) Km for Na+ was not changed; and 5) the half time for the inhibition varied as a function of amiloride concentration or pharmacologic activity of its analogues. On the basis of the above findings, these tyrosine-specific reagents are believed to be useful chemical probes for the identification and characterization of Na+ channel protein.
Prostaglandin synthesis by isolated rat glomeruli: effect of angiotensin II
Authors: Schlondorff D. , Roczniak S. , Satriano J. A. , Folkert V. W.
Published: December 2017

Prostaglandins play a role in the regulation of renal blood flow and glomerular filtration. In the presence of [14C]arachidonate the pattern of prostaglandins produced by isolated glomeruli was PGF2 alpha > PGE2 > PGD2 = TXB2 = 6-keto-PGF1 alpha (a metabolite of prostacyclin). Glomeruli prelabeled with [14C]arachidonate showed an additional labeled prostaglandin that co-chromatographs with 6,15-diketo-13,13-dihydro-PGF1 alpha and may represent breakdown product of prostacyclin. Thus, prostacyclin, judged by its breakdown products, was the second most abundant prostaglandin produced. These results were confirmed by specific radioimmunoassays for PGF2 alpha, PGE2, and 6-keto-PGF1 alpha. Isolated glomeruli produced 1,740 pg x 10 min-1 x mg protein-1 of PGF2 alpha, 798 of 6-keto-PGF1 alpha, and 266 od PGE2. In prelabeled glomeruli angiotensin II causes a small but significant increase in 14C-labeled prostaglandins. Radioimmunoassay for 6-keto-PGF1 alpha showed that the angiotensin stimulation was specific for prostacyclin. Angiotensin II also affected the glomerular handling of [14C]arachidonate. It decreased the uptake of extracellular [14C]arachidonate and increased the incorporation of intracellular [14C]arachidonate into glomerular phospholipids. Based on these results, we propose that in the glomerulus angiotensin increases prostaglandin synthesis and stimulates deacylation and reacylation of phospholipids.
Natriuretic effect of oxytocin on saline-expanded neonatal dogs
Authors: Kleinman L. I. , Banks R. O.
Published: December 2017

The natriuretic effect of oxytocin was studied in 40 anesthetized newborn dogs 2–33 days of age. After saline expansion, puppies excreted only 2.86% of the filtered sodium (adult dogs undergoing similar volume expansion excrete about 65–8% of the filtered sodium). After oxytocin was infused in these saline-expanded puppies at 8 mU x kg-1 x h-1, fractional sodium excretion increased to 7.51%. Oxytocin had no natriuretic effect in nonexpanded puppies. In nonexpanded animals, when distal nephron function was blocked by a combination of ethacrynic acid, chlorothiazide, and amiloride, fractional sodium excretion averaged 31%. In contrast, distal nephron blockade in saline-expanded animals resulted in fractional sodium excretion of 55%. When oxytocin was infused in either saline-expanded or nonexpanded puppies undergoing distal nephron blockade, there was no increase in sodium excretion. These results support the following conclusions. In the newborn dog 1) the attenuated natriuretic response to saline expansion is related to increased reabsorption of sodium in the distal nephron; 2) an adult type of natriuretic response to saline expansion can be induced in puppies by infusion of oxytocin; and 3) oxytocin inhibits sodium reabsorption in the distal nephron.
Renal nerves and catecholamine excretion
Authors: Morgunov N. , Baines A. D.
Published: December 2017

To determine which neurotransmitters are released into urine by renal nerves, we either acutely denervated one kidney or stimulated renal nerves by activation of the baroreflex. Acute denervation increased dopamine (DA) and decreased norepinephrine (NE) excretion from the denervated kidney. In contrast, DA excretion decreased and NE excretion increased progressively from the contralateral innervated kidney. Sodium excretion related directly to DA and inversely to NE excretion. In chronic denervation experiments, baroreceptor stimulation increased NE excretion by 25% more from the innervated kidney than from its contralateral denervated mate, while DA excretion increased by 50% only from the innervated kidney. Baroreflex-stimulated NE and DA excretion from innervated kidneys was reduced by prior feeding of a low salt diet. The response was completely abolished by a high salt diet. Sodium excretion increased by the same proportion from innervated and chronically denervated kidneys following baroreceptor stimulation. In conclusion, 1) renal nerves release both NE and DA, 2) after acute unilateral denervation sodium excretion related directly with DA and inversely with NE excretion, and 3) urinary excretion of NE and DA derived from renal nerves was influenced by dietary sodium intake.
Effect of saline expansion on peritubule capillary pressures and reabsorption
Authors: Ott C. E.
Published: December 2017

The effect of extracellular volume expansion on transcapillary Starling forces, capillary uptake, and the reabsorption coefficient in the peritubule microcirculation of the dog kidney was examined. Micropuncture techniques were used to obtain measurement before and after 4% body wt expansion with isotonic saline. Extracellular volume expansion significantly changed all Starling pressures and capillary uptake. Efferent arteriolar oncotic pressure, interstitial oncotic pressure, and capillary uptake decreased (33.1 +/- 3.3 to 22.1 +/- 4.1 mmHg; 5.2 +/- 0.4 to 4.0 +/- 0.3 mmHg; and 44.9 +/- 9.2 to 28.7 +/- 8.6 nl/min, respectively), whereas capillary hydrostatic pressure and interstitial hydrostatic pressure increased (11.3 +/- 1.2 to 13.7 +/- 1.4 and 5.9 +/- 1.0 to 10.4 +/- 1.2 mmHg, respectively). The calculated reabsorption coefficient was 2.40 during hydropenia and 2.36 nl . min-1 . mmHg-1 following volume expansion. The results show that extracellular volume expansion significantly depresses capillary uptake in the dog and suggest that the decreased uptake can be accounted for totally by changes in transcapillary pressures and a constant reabsorption coefficient.
Lack of evidence for gastrointestinal control of sodium excretion in unanesthetized rabbits
Authors: Obika L. F. , Fitzgerald E. M. , Gleason S. D. , Zucker A. , Schneider E. G.
Published: December 2017

Experiments were performed to determine whether unanesthetized rabbits exhibit a greater natriuresis after oral administration of a hypertonic sodium chloride solution (1.5 mmol NaCl/kg) than after the intravenous administration of the same solution. Male rabbits (New Zealand) were placed on a low sodium diet for 4 days, and on the fifth day a hypertonic NaCl solution (616 mM) was given either by stomach tube (GI) or intravenously (IV), while an equal volume of a hypotonic NaCl solution (31 mM) was given by the alternate route. The studies were repeated on each rabbit so that paired observations were obtained. No differences in plasma Na concentration, peripheral hematocrit, or urinary sodium excretion were observed between the GI and IV groups after administration of the hypertonic NaCl solution. In seven rabbits that were permitted access to food and water following NaCl administration by either route, urinary sodium excretion tended to be reduced (P = 0.08), but, again, no significant differences in plasma sodium concentration, peripheral hematocrit, or urinary sodium excretion were observed between the GI and IV routes of sodium administration. Accordingly, we could find no evidence to support the existence of a GI or portal Na receptor system that regulates urinary sodium excretion in the unanesthetized rabbit.
Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit
Authors: Bradbury M. W. , Cserr H. F. , Westrop R. J.
Published: December 2017

Lymph from the jugular lymph trunks of anesthetized rabbits has been continuously collected and radioiodinated albumin (RISA) therein estimated after microinjection of 1 microliter of 131I-albumin into the caudate nucleus, after single intraventricular injections, and during intraventricular infusions. Comparison of lymph at 7 and 25 h after intracerebral microinjection with efflux of radioactivity from whole brain suggests that about 50% of cleared radioactivity goes through lymph. Concentrations, normalized to cerebrospinal fluid (CSF), were much higher in lymph and retropharyngeal nodes after brain injection than after CSF injection or infusion. Also after brain injection, lymph and nodes contained more activity on injected side in contrast to lack of laterality after CSF administration. Calculation suggests that less than 30% of RISA cleared from brain can do so via a pool of well-mixed CSF. Analysis of tissues is compatible with much RISA draining by bulk flow via cerebral perivascular spaces plus passage from subarachnoid space of olfactory lobes into submucous spaces of nose and thus to lymph.