bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of filtration rate in sodium-depleted and -expanded dogs
Authors: Marchand G. R. , Burke T. J. , Haas J. A. , Romero J. C. , Knox F. G.
Published: December 2017

Sodium balance may affect the response of single-nephron filtration rate (SNFR) to changes in renal arterial pressure (deltaRAP) when the SNFR is measured in the absence of orthograde fluid delivery from the proximal tubule. This thesis was tested in sodium-depleted and -expanded dogs given furosemide, Doca, and low- or high-salt diets, respectively. After 7 days of treatment, renal renin content was significantly greater in the sodium-depleted group (delta = 23.5 +/- 7.4 DU [dog units]/g kidney). Glomerular filtration rate and renal plasma flow were similar in both groups following changes in RAP of 29 +/- 4 and 29 +/- 3 mmHg in the sodium-depleted and -expanded groups, respectively. SNFR at high RAP was not different from SNFR at low RAP in the sodium-depleted group (delta = -0.2 +/- 4.9 nl/min) and slightly, but significantly, greater in the sodium-expanded group (delta = 7.6 +/- 2;1 nl/min). However, the response of SNFR was similar to that of whole-kidney filtration rate. Furthermore, the autoregulatory response (deltaSNFR/deltaRAP) was not significantly different between the groups but was significantly greater than the response calculated for RAP below the range studied. It is concluded that an autoregulatory response of SNFR, in the absence of orthograde fluid delivery from the proximal tubule, is observed in both sodium-depleted and -expanded dogs.
Autoradiography of the water compartments in developing teeth of young mice
Authors: Lyman G. E. , Waddell W. J.
Published: December 2017

The distribution of [14C-a1acetyl-4-aminoantipyrine ([14C]NAAP), as indicators of total tissue water, and [carboxy-14C]inulin ([14C]inulin), as an indicator of extracellular water, were studied by autography in mice 4-16 days old. An autographic technique was used that does not translocate or remove the radioactive material. Photometric densities of the autoradiographs revealed wide variations in radioactivity among the various areas of the teeth. Evidence for binding of [14C]urea to bone limits the usefulness of this compound as an indicator. Although [14C]inulin appeared to be a reliable indicator, it is difficult to correlate its distribution with the progress of mineralization determined by electron microprobe analysis. [14C]NAAP was considered to be the most reliable indicator; it revealed that the water content of various areas of the teeth ranged from 7 to 100% of that in blood.
Renin-angiotensin system and aldosterone secretion during aortic constriction in the rat
Authors: Freeman R. H. , Davis J. O. , Spielman W. S.
Published: December 2017

Suprarenal aortic constriction sufficient to reduce renal perfusion pressure by approximately 50% increased aldosterone secretion in anesthetized rats pretreated with dexamethasone. Bilateral nephrectomy under the same experimental conditions blocked the aldosterone response. Additionally, [1-sarcosine, 8-alanine]angiotensin II blocked the response in aldosterone secretion to aortic constriction in dexamethasone-treated rats. Finally, in rats hypophysectomized to exclude the influence of ACTH, the aldosterone response to aortic constriction was blocked by [1-sarcosine, 8-alanine]angiotensin II. The results indicate that angiotensin II increased aldosterone secretion during aortic constriction in the rat. These observations, along with those reported previously in sodium-depleted rats, point to an important overall role for the renin-angiotensin system in the control of aldosterone secretion in the rat.
Sugar interaction with the antiluminal surface of the proximal tubule in dog kidney
Authors: Silverman M.
Published: December 2017

The pulse-injection multiple-indicator-dilution technique in vivo has been used to investigate bidirectional sugar interaction with the antiluminal surface of the nephron in dog kidney. Simultaneous renal vein and urine outflow curves were obtained for radiolabeled sugars known to interact with the antiluminal surface. The following sugars were tested relative to T-1824 albumin (plasma reference) and creatinine (extracellular reference) under conditions of high-dose phlorizin preloading (75–225 mg/kg): D-glucose, D-xylose, D-fucose, D-mannose, D-galactose, L-arabinose, myoinositol, and D-fructose. The results indicate that as the plasma concentration of phlorizin increases there is, first, a partial inhibition of sugar interaction at the antiluminal membrane so that only unidirectional uptake of sugar from blood to tubular cell is observed, followed by complete inhibition of sugar interaction at the peritubular face of the antiluminal membrane, resulting in superposition of sugar and creatinine curves in the renal vein effluent. Two possible interpretations exist. i) Phlorizin exerts its inhibitory action successively at the cytoplasmic and then at the peritubular face of the antiluminal membrane. Moreover, since all of the sugar substrates are inhibited by phlorizin, the data suggest that the sugar-membrane interaction takes place at a common site at the level of the proximal tubule. ii) Alternatively, the action of phlorizin could result from a metabolic inhibitory effect affecting multiple sugar transport systems at the antiluminal membrane.
Natriuresis after adrenal enucleation: effect of spironolactone and dexamethasone
Authors: Bengele H. H. , McNamara E. R. , Alexander E. A.
Published: December 2017

After adrenal enucleation, rats have an impaired ability to excrete a salt load because of enhanced collecting duct reabsorption. This antinatriuretic effect, thought to be secondary to a mineralocorticoid-like substance secreted by the enucleate gland, can be reversed by treatment with spironolactone or dexamethasone. To define the renal mechanisms involved in this drug-induced natriuresis we have utilized clearance and micropuncture techniques in enucleate saline-expanded rats that were treated with either spironolactone (S) or dexamethasone (D), or were untreated (U). Sodium excretion was clearly increased after S, 13.9, and D, 19.3 mueq/min vs. u, 5.9 mueq/min. The mechanisms of this natriuresis, however, were dissimilar. Spironolactone-treated rats were not different from untreated rats except with regard to function beyond the superficial late distal tubule, where U rats reabsorbed over 50% of the delivered sodium. In the S group 38% of the excreted sodium was added along this tubular locus, 5.2% of the filtered sodium reaching the late distal tubule and 7.3% appearing in the urine. These data demonstrate that the natriuresis after S is secondary to the net addition of sodium beyond the superficial late distal tubule. Spironolactone may work by inhibiting a mineralocorticoid-like product of the enucleate gland and, thereby, eliminate the sodium-retaining effect of this product. The natriuresis after D, however, can be explained solely on the basis of a markedly increased filtered load of sodium traversing the nephron.
Effect of the ionophore A23187 on chloride transport across isolated frog cornea
Authors: Candia O. A. , Montoreano R. , Podos S. M.
Published: December 2017

The ionophore A23187 at a concentration of 10(-7) to 10(-5) M stimulated active transport of Cl across the isolated frog cornea. The ionophore had no effect in a Cl-free medium. Both unidirectional Cl fluxes were increased by A23187. The electrical resistance was decreased, and this can be totally accounted for by the increment in passive Cl fluxes. The effect of A23187 on Cl transport and permeability mimicked the effects of cyclic AMP, isoproterenol, and epinephrine. A23187 had no effect when the corneas were fully stimulated by epinephrine or isoproterenol. A23187 produced normal stimulation of the SCC in corneas pretreated with alpha- and beta-adrenergic blockers. The stimulation of the SCC by A23187 was dependent on the presence of Ca in the Ringer solution. Excess Ca (10 mM) resulted in a reduced response. Increasing the Mg concentration in the medium reduced the stimulation of the SCC with Ca concentrations of 0.1-5 mM, but prevented the relative inhibition of 10 mM Ca. Intracellular Ca concentration seemed to regulate Cl permeability of the cornea.
Aldosterone and postprandial renal excretion of sodium and potassium in sheep
Authors: Rabinowitz L. , Denham S. C. , Gunther R. A.
Published: December 2017

When sheep rapidly eat a meal of dry feed a period of antinatriuresis and antidiuresis is rapidly initiated and lasts for 2–3 hrs. This is followed by a postprandial period of natriuresis and diuresis. This study tested the hypothesis that the postprandial natriuresis was due to a reduction in the secretion of aldosterone. In unanesthetized ewes of about 50 kg body wt, measurements were made of sodium and potassium excretion beginning in the terminal phase of the feed-induced antinatriuresis and continuing through the period of postprandial natriuresis. Aldosterone, given by constant infusion at a physiological dose (10 microgram/h), inhibited the natriuresis. Spironolactone, a competitive inhibitor of aldosterone given as a single intravenous injection of 5 mg/kg body wt, did not significantly increase the natriuresis. These results support the stated hypothesis. Neither aldosterone nor spironolactone had a significant effect on potassium excretion. This finding supports earlier view that aldosterone has only a small role in the homeostatic control of potassium excretion in sheep.
Renal concentrating ability in the uninephrectomized rat
Authors: Sachtjen E. , Rabinowitz L. , Binkerd P. E.
Published: December 2017

To investigate the effects of uninephrectomy on renal concentrating ability, studies were performed on unanesthetized rats 5-11 days after uninephrectomy (UN) or a sham operation (SO). Female rats were deprived of water for 27 h prior to the infusion of inulin and para-aminohippurate and urine collection. They were also preconditioned to being handled and to the experimental locale. During a nondiuretic state urine osmolality was the same for all UN and SO groups (mean about 1,700 micro osmol/g H2O), whereas the mean solute excretion rate (micro osmol/min per kg body wt per kidney) was 74 in the UN and 35 in the SO rats. When SO rats were infused with mannitol or isotonic saline to increase their solute excretion rate per kidney to the level of the UN rats, urine osmolality dropped 200-1,000 micro osmol/g H2O; when urea was infused, urine osmolality did not drop. Thus, after uninephrectomy and a consequent doubling of the solute excretion rate per kidney, renal concentrating ability was higher than predicted on the basis of a comparable but acute elevation of the solute excretion rate. The glomerular filtration rate was about 17 ml/min per kg body wt in the SO rats and was 1.2 times greater (on a per kidney basis) in the UN rats. These exceptionally high glomerular filtration rats are attributed to preexperimental conditioning of the rats and the absence of stress during urine collection.
Structural and functional heterogeneity of mammalian nephrons
Authors: Valtin H.
Published: December 2017

Since the anatomical descriptions of Bowman showing differences between nephrons originating in the superficial and deep cortex, the concept of heterogeneity has been extended from identification of dissimilarities between nephrons to recognition of inhomogeneity within major portions of individual nephrons. We are now aware of functional correlates for the anatomical differences between nephrons, between analogous parts of different nephrons, and between the three portions of the proximal tubule and the three or more parts of the distal tubule. The implications of all of these differences for major renal processes, such as isosmotic fluid transport, salt balance, hypertension, urinary acidification, and the concentration or urine are now being defined. It seems likely that new conceptual and technical approaches, especially electron probe microanalysis, will add appreciably to defining the role of heterogeneity in these and other processes. Despite the increasing complexity of nephron heterogeneity, it is recommended that our basic nomenclature be retained and that new findings be incorporated into the schema set forth by Karl Peter. It would be very helpful if reports of investigations on single nephrons or segments of nephrons were to include diagrams delineating the structures on which the work was performed.
Effects of surgery on plasma volume and salt and water excretion in rats
Authors: Maddox D. A. , Price D. C. , Rector F. C.
Published: December 2017

Surgical preparation of rats for micropuncture resulted in a marked decrease in sodium excretion (UNaV) compared to awake animals. Associated with surgery, hematocrit (Hct) rose. Studies were performed to determine whether the rise in Hct resulted from reduced plasma volume (PV) or increased red cell volume (RCV) and to explore the relation of such alterations to the fall in UNaV. PV and RCV were determined in the calm awake rat using 125I-albumin and 51Cr-labeled red blood cells. Micropuncture surgery was performed and RCV, PV, and Hct again measured. After anesthesia and femoral artery catheterization, Hct was not different from Hct in awake animals (42.9 ++/- 2.8%). The Hct increased following surgery to 48.2 +/- 2.8% (P less than 0.001), accompanied by a large fall in PV (-18.9 +/- 2.3%, P less than 0.001) with no change in RCV. Plasma volume repletion to awake values restored UNaV toward levels appropriate for dietary intake in animals on a high salt diet. Althouth plasma repletion slightly increased UNaV above awake values in low salt diet rats, they continued to avidly retain salt with respect to total salt load.
Vasopressin responsiveness of renal adenylate cyclase in newborn rats and rabbits
Authors: Schlondorff D. , Weber H. , Trizna W. , Fine L. G.
Published: December 2017

Newborns show an inability to concentrate maximally their urine. The vasopressin responsiveness of adenylate cyclase was, therefore, examined in membranes obtained from kidneys of neonatal and adult rats and from renal medulla and isolated collecting tubules of newborn and adult rabbits. In spite of higher basal and NaF-stimulated activity, vasopressin failed to stimulate adenylate cyclase from neonatal rat kidneys. In neonatal and adult rabbits, basal and NaF-stimulated adenylate cyclase activities of renal medullary membranes were comparable but vasopressin stimulation was significantly lower in the newborns. No change in hormonal activation constant was observed. This hyporesponsiveness of neonatal adenylate cyclase to vasopressin was confirmed with single isolated rabbit collecting tubules for adenylate cyclase determination, a highly sensitive preparation. It is intriguing to speculate that the low vasopressin stimulation of the medullary adenylate cyclase in the developing kidney may contribute to the known limitations of the urinary concentrating mechanism in the newborn period.
Current concepts on the pathophysiology of acute renal failure
Authors: Stein J. H. , Lifschitz M. D. , Barnes L. D.
Published: December 2017

In the pase decade, several experimental models of acute renal failure (ARF) have been evaluated with micropuncture and hemodynamic techniques. Five of these models have been most extensively studied: glycerol injection, renal artery clamping, intrarenal norepinephrine infusion, uranyl nitrate, and mercuric chloride administration. In the first three models, renal ischemia is the initiating insult, whereas in the two nephrotoxic models a direct effect of the agent on cellular integrity is also seemingly operative. In all of these models, renal blood flow 24--48 h after the initial insult either spontaneously returns to normal or can be elevated to this level with volume expansion but without restoration of the glomerular filtration rate. Therefore, the maintenance of ARF in these various models is due to other factors, which include tubular obstruction, leakage of filtrate across damaged tubular epithelium, and a decrease in the glomerular capillary ultrafiltration coefficient. In a given model, one or all three of these alterations may be present. Although these various models may not be completely analogous to the clinical setting, they have provided powerful tools for the study of ARF and their use has greatly increased our knowledge in this field.
Volume absorption in the pars recta. III. Luminal hypotonicity as a driving force for isotonic volume absorption
Authors: Andreoli T. E. , Schafer J. A.
Published: December 2017

This paper examines the possibility that osmotic disequilibrium between luminal and bathing solutions may account for isotonic fluid absorption coupled to active Na+ absorption observed when superficial proximal straight tubules isolated from rabbit kidney are perfused and bathed with NaCl solutions in the absence of CO2, HCO3-, and luminal organic solutes. If luminal hypotonicity provides a driving force for isotonic fluid absorption under these conditions, the luminal fluid must be nearly isotonic; and steady-state luminal hypotonicity should develop sufficiently rapidly that the absolute rate of volume absorption ('JV, nl min-1) coupled to active Na+ transport is relatively independent of perfusion rate, so that the normalized rate of fluid absorption (JV, nl min-1 mm-1) is approximately constant. Our theoretical calculations indicate that these expectations are fulfilled. A 0.42-0.56 mM reduction in luminal NaCl concentration adequately accounts for the JV observed under such conditions, because of the high hydraulic conductivity of these tubules; and within the range of tubule lengths normally employed with isolated proximal straight tubules, JV is relatively indepedent of perfusion rate within the generally observed range of experimental error.
Effect of potassium on proximal tubular function
Authors: Cardinal J. , Duchesneau D.
Published: December 2017

In order to study the effect of potassium on the renal tubule, proximal convoluted tubules were dissected from rabbit kidneys and perfused in vitro. Omitting potassium from both the perfusate and bath caused the rate of fluid absorption and the transtubular potential difference to fall to zero. This effect was due to the absence of potassium in the bathing medium since no change was observed when potassium was omitted from the perfusate only. With 0.5 and 1.0 meq/liter of potassium in the bath, there was still a significant decrease from control in both the potential difference and the rate of fluid absorption. With 2.5 meq/liter of potassium in the bath, the results did not differ from control. In further studies, tubules were perfused with 10 meq/liter of potassium in both perfusate and bath. There was no change in the potential difference of fluid absorption. These results are consistent with the view that active transtubular transport of sodium is linked to the influx of potassium into the cell at the peritubular membrane and that this is probably mediated by sodium-potassium-ATPase. Our results also suggest that the variations of potassium concentration in the physiological range do not affect proximal tubular function.
Glomerular permselectivity: barrier function based on discrimination of molecular size and charge
Authors: Brenner B. M. , Hostetter T. H. , Humes H. D.
Published: December 2017

The formation of glomerular ultrafiltrate is dependent on the interplay of glomerular pressures and flows as well as the intrinsic permselectivity properties of the glomerular capillary wall. These intrinsic permeability properties serve to exclude macromolecules from the urinary space, based on size as well as net molecular charge discrimination. Neutral dextrans with molecular radii less than 20 A cross the glomerular wall without measurable restriction, whereas dextrans with radii greater than 42 A are almost completely barred. For any given size, negatively charged macromolecules are restricted to a greater extent than neutral molecules. Additionally, positively charged molecules are enhanced in their ability to cross the glomerular wall compared to similarly sized neutral polymers. The concept of a charge barrier, due to fixed negative charges within the glomerular wall, is also supported by morphological studies. Glomerular injury, leading to proteinuria, has been associated with loss of the charge-selective properties of these capillaries. Loss of glomerular fixed negative charges may also result in the foot process fusion and mesangial cell dysfunction often observed in proteinuric states.
Magnesium metabolism in potassium-depleted rats
Authors: Duarte C. G.
Published: December 2017

In rats, a diet depleted of potassium caused a significant hypokalemia and hypermagnesemia, a diuresis and natriuresis, a decrease in urinary and fecal excretion of potassium, a magnesiuria, and a decrease in fecal excretion of magnesium. Balance studies revealed that potassium metabolism was negative in potassium-depleted rats and that magnesium metabolism was positive and higher than in control rats. In potassium-depleted rats, potassium and magnesium contents in muscle were reduced, whereas the sodium level was increased and plasma aldosterone was significantly lower. Therefore, the elevation in plasma concentration of magnesium induced by a diet poor in potassium is the result of a more positive metabolic balance of magnesium and of shifting of magnesium from the tissue into the plasma compartment. Results of additional preliminary studies support the possibility that the hypermagnesemia may be mediated through the depression in mineralocorticoid activity induced by the depletion of potassium.
Principles of nephron differentiation
Authors: Michael H.
Published: December 2017

Differentiation of cell function should be studied in homogeneous cell populations. The differentiating mammalian kidney is a thoroughly heterogeneous organ. Consequently, the single epithelial segment was studied in situ and, particularly, by in vitro analysis of physical, chemical, and ultrastructural phenomena in perfused and nonperfused dissected nephrons. Results: The changes of hydraulic permeability in the proximal nephron appear to be important in utilizing extracellular forces for absorption, since cellular transport is restricted by low basolateral membrane area and by ion pump sites (Na+-K+-ATPase). Salt transport in the diluting segment, by contrast, changes at constant osmotic permeability and at increasing ion concentration gradients across the epithelium. Extracellular volume and osmotic homeostasis in the neonate testify to the competence of organ function, although cell structure and function differentiate. In the future, interactions between nephron cell functions will be studied by altering the natural sequence of phenomena during differentiation.
Glomerulotubular balance following saline loading in the developing canine kidney
Authors: Arant B. S.
Published: December 2017

Glomerulotubular relationships for glucose were studied in the developing kidney before and after saline loading in 13 anesthetized puppies that were 2–51 days of age and in one adult. When volume expansion, plasma glucose concentrations of more than 500 mg/dl, and changes in sodium excretion (FENa) were avoided, the ratio of maximal tubular reabsorption of glucose (TmGlc)/inulin clearance (CIn) was 3.37 +/- 0.28 (means +/- SD) in the puppies and did not change with age. Following intravenous saline loading (20 ml/kg), TmGlc and sodium reabsorption decreased, CIn decreased, and TmGlc/CIn decreased to 2.97 +/- 0.67. When a volume equivalent to the saline load had been excreted, TmGlc increased, CIn and FENa did not change, and TmGlc/CIn increased to 3.60 +/- 1.00. Splay in the glucose titration curve did not change with age, but the portion of the curve at saturation decreased with saline loading and returned to the control pattern as the saline load was excreted. It is concluded that glomerulotubular balance for glucose obtains from birth in the dog kidney, and that saline loading results in functional glomerulotubular imbalance with glomerular preponderance and alters the appearance of the glucose titration curve.
Bidirectional sodium fluxes across the placenta of conscious sheep
Authors: Weedon A. P. , Stacey T. E. , Ward R. H. , Boyd R. D.
Published: December 2017

Conscious pregnant sheep in the last 3 wk of gestation were studied 1––3 days after surgery. Fetal plasma sodium concentration was significantly lower than maternal. A mean electrical potential difference (PD) of 34 +/- 4 (SE) mV (n = 24) was recorded between maternal and fetal intravascular catheters, the mother being positive with reference to fetus. Unidirectional fetomaternal (Jf leads to m) and maternofetal (Jm leads to f) sodium fluxes were determined by application of Fick's principle to uterine and umbilical circulations following injection of 22NaCl or 24NaCl to fetus or mother, respectively. Blood flows were measured by an antipyrine technique. Jm leads to f = 0.142 +/- 0.029 mmol/min (n = 10); Jf leads to m =0.137 +/- 0.015 mmol/min (n = 21). Jm leads to f increased as a linear function of calculated fetal weight. In seven sheep both Jm leads to f and Jf leads to m were measured in a single experiment. The measured ratio Jm leads to f/Jf leads to m was significantly different from the ratio predicted using Ussing's flux ratio equation. There is probably a transplacental sodium pump active in the direction fetus to mother.
Possible roles for microtubules and microfilaments in ADH action on toad urinary bladder
Authors: Kachadorian W. A. , Ellis S. J. , Muller J.
Published: December 2017

Intramembranous particle aggregates in the luminal membrane of toad bladder granular cells after vasopressin stimulation have been found to correlate closely and specifically with induced alterations of water permeability. Roles for microtubules and microfilaments in mediating the latter response have been proposed on the basis of studies involving colchicine and cytochalasin B, respectively. In the present investigation the effects of these agents on both initiating and sustaining vasopressin-induced osmotic water flow and the particle aggregation phenomenon were studied. The results indicate that during initiation the aggregation and water flow responses to vasopressin are each colchicine- and cytochalasin B-sensitive and that these sensitivities can be wholly additive. However, after full vasopressin stimulation is established, the same responses demonstrate sensitivity only to cytochalasin B, not to colchicine. The findings, therefore, suggest that microtubules and microfilaments may be independently necessary for the initiation of the aggregation and water flow responses to vasopressin, and that microfilaments, but not microtubules, are required for their maintenance.
Osmotic and nonosmotic control of vasopressin release
Authors: Schrier R. W. , Berl T. , Anderson R. J.
Published: December 2017

While the existence of an osmotic control for vasopressin (AVP) release has been long recognized, development of a sensitive immunoassay has allowed for better understanding of factors affecting the threshold and sensitivity of AVP release. Individual variation, genetic, environmental, and species differences, and the nature of the solute providing the osmotic stimuli can significantly affect the release of the hormone by altering the threshold and/or the sensitivity of the osmoreceptor. In addition to the hypothalamic osmoreceptor, AVP secretion is also controlled by an anatomically separate pathway which is responsive to nonosmotic stimuli. It appears that both low-pressure (left atrial) and high-pressure (carotid and aortic) receptors via the parasympathetic pathways provide the major nonosmotic pathway for vasopressin release. Such pathways are activated in response to acute systemic hemodynamic changes, stress, and hypoxia. The precise interaction between osmotic and nonosmotic AVP release remains to be clarified. A model of osmotic and nonosmotic interactions, based on available electrophysiologic studies, is presented and its clinical implications are discussed.
Effect of parathyroid hormone on bicarbonate absorption by proximal tubules in vitro
Authors: Iino Y. , Burg M. B.
Published: December 2017

The effect of parathyroid hormone on bicarbonate absorption was tested in rabbit proximal renal tubules perfused in vitro. In proximal straight tubules 0.05 U/ml of parathyroid hormone caused a large and reversible increase in the steady-state bicarbonate concentration in tubule fluid. Further, the rates of bicarbonate and fluid absorption (measured at faster flow rates) were inhibited approximately 50% by the hormone. We conclude that parathyroid hormone directly inhibits fluid and bicarbonate absorption by proximal straight tubules, causing an increase in the bicarbonate concentration in the tubule fluid, and we suggest that this action of the hormone contributes to the increase in renal bicarbonate excretion that is generally caused by the hormone. In proximal convoluted tubules, parathyroid hormone was previously demonstrated by other investigators to inhibit fluid and bicarbonate absorption approximately proportionally, so that there was little or no change in the bicarbonate concentration in tubule fluid. In agreement we found in the present studies that 0.05 U/ml of the hormone did not affect the steady-state bicarbonate concentration in proximal convoluted tubule fluid and that 5 U/ml caused only an equivocal increase in tubule fluid bicarbonate concentration.
Excretion of phenol red by the Necturus kidney
Authors: Tanner G. A. , Carmines P. K. , Kinter W. B.
Published: December 2017

Phenol red (phenolsulfonphthalein, PSP) is thought to be secreted by proximal kidney tubules in all vertebrates. The present study examined PSP transport by the kidney of the salamander, Necturus maculosus. In Necturus kidneys perfused with oxygenated Ringer solution, the PSP/creatinine clearance ratio was unity. Perfusion with 1 mM octanoate converted net p-aminohippurate (PAH) reabsorption to net secretion, but had no effect on PSP. In seven urethan-anesthetized Necturi, the PSP/inulin clearance ratio averaged 0.85 +/- 0.21 (SD), not significantly different from unity. Thin slices from Necturus kidneys incubated in vitro for 2 h failed to accumulate PSP; slice-to-medium (S/M) concentration ratios averaged 0.8 +/- 0.2 (n = 6). With frog kidney slices, (S/M)PSP was 9.6 +/- 1.4 (n = 6). Necturus kidney slices accumulated PAH ((S/M)PAH = 4.1 +/- 0.7) (n = 6), but uptake was not inhibited by 1 mM PSP. We conclude that Necturus kidney tubules transport PAH, but do not transport PSP. These results are consistent with the hypothesis that the organic acid secretory system in most animals involves several carriers.
Impaired renal bicarbonate reabsorption in the hypothyroid rat
Authors: Michael U. F. , Kelley J. , Vaamonde C. A.
Published: December 2017

We previously demonstrated a decrease of sodium reabsorption in the proximal superficial nephron of the hypothyroid rat. The present clearance studies were designed to examine the renal handling of bicarbonate in hypothyroid rats. Hypothyroidism was induced by the intraperitoneal injection of Na131I and the animals were studied 10 or more wk thereafter under anesthesia and compared to their age-matched litter-mates. As is characteristic of hypothyroid animals, insulin clearance was lower and fractional urine flow and sodium excretion rates were higher than in the control rats. At the peak of the bicarbonate diuresis and at similar blood pH, PCO2, and bicarbonate levels, fractional renal bicarbonate excretion was significantly higher in the hypothyroid animals: 22 +/- 2 vs. 15 +/- 1%, P less than 0.02. This perturbation of bicarbonate reabsorption of the hypothyroid rats was independent of the influence of extracellular fluid volume expansion and appears closely related to the impaired sodium reabsorptive capacity characteristic of experimental hypothyroidism.
Renal vascular resistance and reactivity in the spontaneously hypertensive rat
Authors: Fink G. D. , Brody M. J.
Published: December 2017

Renal vascular resistance is elevated in spontaneously hypertensive rats (SHR) when compared to normotensive control Wistar-Kyoto rats (WKY). The present study examined possible determinants of this raised vascular resistance in in situ autoperfused kidneys of pentobarbital-anesthetized, 12- to 16-wk-old SHR and WKY. Over a wide range of arterial pressures (30––100 mmHg) renal blood flow was consistently higher in WKY than in SHR. This relative flow difference was unchanged by acute renal denervation, with renal vascular resistance decreasing approximately 20% in both strains. Changes in renal vascular resistance to renal nerve stimulation and the administration of intra-arterial vasoactive hormones also were assessed. Vascular responses to renal nerve stimulation, tyramine, angiotensin II, and acetylcholine were similar in kidneys of the two strains, but reactivity to norepinephrine was significantly less in kidneys of SHR. It was concluded that elevated renal vascular resistance in the SHR does not result from an excessive neurogenic influence on the renal vasculature or from vascular hyperreactivity to norepinephrine or angiotensin II.
Effect of arsenite on renal tissue slice metabolism in chronic metabolic acidosis and alkalosis
Authors: Simpson D. P. , Hecker J.
Published: December 2017

Tissue slices prepared from renal cortex of littermate dogs with chronic metabolic acidosis or alkalosis were incubated in media with or without arsenite and containing 1 mM L-[14C]glutamine or [1,5–14C]citrate. The presence of arsenite increased the concentration of alpha-ketoglutarate in slices by 5––20 times the values found without this inhibitor. alpha-Ketoglutarate concentrations in acidotic slices were 40% or more greater than those in alkalotic ones when arsenited was present. 14C incorporation into alpha-ketoglutarate was also increased manyfold by arsenite with either labeled glutamine or citrate as substrate. 14CO2 production from labeled glutamine by over 90% and from labeled citrate by over 75%; the difference between 14CO2 production by acidotic and alkalotic slices was greatly reduced or eliminated by arsenite. These results suggest that in chronic metabolic acidosis metabolism of both glutamine and citrate is stimulated at a site or sites preceding formation of alpha-ketoglutarate.
Effects of kidney tubule obstruction on glomerular function in rats
Authors: Tanner G. A.
Published: December 2017

The effects of chronic blockade of single kidney tubules on glomerular capillary pressure (GCP) and blood flow were examined in anesthetized rats. Tubule blockade with castor oil for 24 h decreased GCP from 48.0 +/- 3.8 to 39.5 +/- 4.7 mmHg (P less than 0.001). The full decrease in GCP observed at 24 h was apparent by about 12 h. Bilateral ureteral obstruction for 24 h prevented a decrease in GCP. Nonradioactive microspheres (8.4 +/- 0.84 micron diam) were used to assess relative blood flow to blocked and normal nephrons. These microspheres were completely extracted by rat kidneys and had no effect on total renal blood flow. The ratio of microsphere counts in glomeruli of blocked versus normal nephrons averaged 0.61 +/- 0.21, indicating a significantly (P less than 0.001) decreased glomerular blood flow in nephrons obstructed for 24 h. Since both GCP and blood flow were reduced after tubule obstruction, afferent arteriolar constriction is involved. The data suggest a local mechanism activated by prolonged tubule blockade which shifts filtrate formation and blood flow away from blocked nephrons.
Hemodynamic and excretory response of the neonatal canine kidney to acute volume expansion
Authors: Goldsmith D. I. , Drukker A. , Blaufox M. D. , Edelmann C. M. , Spitzer A.
Published: December 2017

It is generally recognized that developing animals retain sodium due to an enhanced reabsorption in distal tubule segements, even when the amount administered is in excess of their needs. This study was designed to test the relationship between this relative inability to dispose of a saline load and the functional characteristics of the kidney during postnatal maturation. In addition, we explored the role played by some of the factors known to affect natriuresis in the adult subject. Measurements of sodium excretion, glomerular filtration rate (GFR), and renal blood flow (RBF) and its intrarenal distribution were made in three age groups of puppies and in adult dogs. During expansion the GFR rose rapidly and to a similar extent at all ages, but it fell thereafter, the rate of decline being much slower in adult than in developing animals (P less than 0.001). RBF and its intrarenal distribution were not altered by volume expansion. The degree of natriuresis did not reflect either the age-related or the expansion-induced changes in GFR. Fractional and absolute sodium excretion were substantially higher in 2-wk-old puppies than in either 1- or 3-wk-old animals (P less than 0.002). These findings demonstrate that the blunted renal response of the maturing animal to saline loading is due to the persistence of an enhanced tubular reabsorption rather than to a limitation in glomerular filtration.
Effects of changes in electrical potential difference on tubular potassium transport
Authors: Garcia-Filho E. , Malnic G. , Giebisch G.
Published: December 2017

To assess directly the role of the transepithelial potential difference (PD) on potassium concentration differences across distal tubular epithelium, continuous and stationary microperfusion experiments were done in tubules voltage-clamped over a wide range of lumen-negative potentials. Potassium was measured either chemically or in situ by potassium-sensitive microelectrodes. Distal cell PD measurements show that most of the potential drop induced by luminal current injection occurred across the luminal cell membrane. Experiments were done in rats either on a control or on a high potassium diet and after amiloride administration. Luminal potassium was highly sensitive to imposed electrical potential changes, attainment of a new steady-state intraluminal potassium concentration was rapid (less than 1 s), and higher luminal potassium concentrations were observed in animals in which potassium secretion had been stimulated. Similar slopes of tubular fluid-to-plasma potassium ratios versus transepithelial potential differences were observed in all experiments. All slopes intersected, at zero PD, at a luminal tubular fluid-to-plasma concentration ratio in excess of unity, indicating the presence of an active component of potassium secretion.
Peritubular uptake and transepithelial transport of glycine in isolated proximal tubules
Authors: Barfuss D. W. , Mays J. M. , Schafer J. A.
Published: December 2017

We examined transport of glycine from the bathing solution into cells and across the epithelium of perfused and nonperfused segments of isolated proximal straight (PST) and proximal convoluted (PCT) tubules. The cell-to-bath distribution ratio in about 0.15 mM glycine was 10.0 +/- 0.7 (SE) in nonperfused PST and 4.3 +/- 1.2 in PCT. Rapid luminal perfusion reduced these values to 4.6 +/- 0.3 and 2.0 +/- 0.5, respectively, but cellular accumulation in the PST still confirmed the presence of active basolateral uptake which was Na+ dependent. Bath-to-lumen glycine fluxes in both segments were linear over a wide range of bathing solution glycine concentrations, and the apparent permeability of this nonsaturable pathway was not significantly different from the nonsaturable component of the lumen-to-bath flux, evaluated by nonlinear fitting. Removal of Na+ from perfusing and bathing solutions reduced the cellular glycine concentration by more than 60% in the PST, yet this had no effect on bath-to-lumen glycine fluxes. We conclude that backleak of glycine occurs by a paracellular path.
Effect of furosemide on thoracic duct lymph flow in the dog
Authors: McCaffrey C. , Levy M.
Published: December 2017

Furosemide 20 mg/kg was given intravenously to 12 anesthetized dogs with clamped renal pedicles. Thoracic duct lymph flow (TDLF) increased promptly by 38% (P less than 0.05), an increment that lasted 80 min. Because in 6 of 12 dogs there was a transient increase in splanchnic blood flow, in separate groups splanchnic blood flow was either markedly constricted or markedly increased by intravenous isoproterenol. Thoracic duct lymph flow increased by 95 and 90%, respectively, following furosemid despite no further change in splanchnic blood flow. Furosemide had no effect on blood pressure, lymph protein, or plasma sodium. In four chronic caval dogs, TDLF was increased by 400%, yet furosemide produced a further increment in lymph flow of 30% (P less than 0.05). Infusion of a 25% albumin solution to contract the interstitial fluid did not abolish the furosemide effect, but a 10% mannitol solution did. Furosemide increased TDLF even after the infusion of papaverine reduced blood pressure to 60 mmHg. We conclude that furosemide increases TDLF by acting directly on splanchnic capillaries to allow increased filtration of fluid in the absence of increased splanchnic blood flow or capillary hydrostatic pressure.
Quantification of renal uric acid synthesis in the rat
Authors: Chin T. Y. , Cacini W. , Zmuda M. J. , Quebbemann A. J.
Published: December 2017

The excretion of nephrogenic uric acid in the urine of Sprague-Dawley rats was estimated by use of the isotope-dilution technique. In nonfasted rats the urine-to-plasma specific activity ratio (SAR) of [14C]uric acid was 0.93, suggesting that a minimum of 7% of the uric acid excreted in the urine is synthesized in the kidney. During hypoxanthine infusion the SAR decreased in a dose-related fashion, indicating that the rat kidney is capable of synthesizing relatively large amounts of uric acid and that circulating precursor levels may in part regulate the renal synthesis of uric acid. During allopurinol infusion the SAR increased to 1.0, demonstrating that the SAR is a valid indicator of the contribution of nephrogenic uric acid excreted into the urine. Results of perfusion studies in isolated rat kidneys suggest that uric acid is the major end product of purine catabolism in the rat kidney and that some uric acid formed in the kidney may be absorbed directly into the circulation.
myo-Inositol transport in renal brush border vesicles and it inhibition by D-glucose
Authors: Hammerman M. R. , Sacktor B. , Daughaday W. H.
Published: December 2017

We examined the mechanism of myo-inositol uptake by rabbit renal proximal tubule brush border membrane vesicles and characterized the relationship between the transports of myo-inositol and D-glucose. A 100 mM Na+ electrochemical gradient (extravesicular medium > intravesicular medium) stimulated the initial rate of myo-inositol uptake 20- to 60-fold. Other cation gradients were ineffective. The Na+ myo-inositol co-transport system was shown to be electrogenic. The Na+ electrochemical gradient-dependent uptake of myo-inositol saturated at about 1 mM myo-inositol, with an apparent Km of 94 micro M at an initial 100 mM Na+ gradient. D-Glucose was an inhibitor of the Na+ gradient-dependent uptake of myo-inositol. D-Glucose, but not L-glucose, elicited accelerative exchange diffusion of myo-inositol. myo-Inositol did not significantly inhibit the Na+ gradient-dependent transport of D-glucose. We suggest that D-glucose inhibits myo-inositol uptake by dissipating the membrane potential and sharing the myo-inositol carrier. The inhibition of myo-inositol transport across the brush border membrane by D-glucose explains how glycosuria could produce inosituria in patients with diabetes mellitus.
Pathways of ion movement in the canine tracheal epithelium
Authors: Welsh M. J. , Widdicombe J. H.
Published: December 2017

The pathways of ion movement across canine tracheal epithelium, a Cl-secreting tissue, were examined by three techniques. First, the measurement of simultaneous, unidirectional fluxes of Na or Cl and mannitol, a large hydrophilic molecule that serves as a marker of the paracellular pathway, indicated that a significant fraction of both the Na flux from submucosa to mucosa (J Na sm) and the flux of Cl from mucosa to submucosa (J Cl ms) traverse the cellular pathway. The ratio of the Na-to-Cl diffusion coefficients through the paracellular pathway was 0.23, in contrast to the free solution ratio of 0.63. Second, in voltage-clamp experiments we examined the effect of transepithelial voltage differences on the unidirectional fluxes of Na and Cl. The results agree with the previous findings, suggesting that there are voltage-independent, or transcellular, backfluxes of Na and Cl, and that the relative permeability of Na to Cl through the voltage-dependent (presumably paracellular) pathway was 0.28. Third, measurement of transepithelial diffusion potentials gave a Na-to-Cl permeability ratio of 0.31 +/- 0.02 (mean +/- SE). These results suggest that there are significant transcellular backfluxes of Na and Cl and that the paracellular pathway in the canine trachea is anion selective. An anion-selective pathway would tend to shunt the secreted Cl back through the paracellular pathway, thus minimizing the net ion and fluid movement across the tissue in the open-circuit condition.
Accumulation of [14C]urate and [3H]PAH in isolated proximal tubular segments of the rabbit kidney
Authors: Schali C. , Roch-Ramel F.
Published: December 2017

Segments of rabbit proximal tubules (S1, S2, and S3) were incubated (30 min, 37 degrees C, pH 7.4) in Ringer solution (under O2) containing [14C]urate or [3H]PAH and probenecid, pyrazinoic acid (PZA), urate, or PAH, all at 1 mM. The ratio [14C]urate (counts/min per nanoliter of tubular cell water)/(counts/min per nanoliter of incubation medium) (T/M) reached 2.92 +/- 0.31 (mean +/- SE; n = 15), 6.08 +/- 0.42 (n = 42), and 1.72 +/- 0.31 (n = 14) for S1, S2, and S3 segments, respectively. In these segments the uptake of [3H]PAH was 22.7 +/- 4.6 (n = 19), 133 +/- 18.9 (n = 24), and 66.2 +/- 15.3 (n =0). The accumulation of [14C]urate was saturated at 2 x 10(-4) M in the medium, and that of [3H]PAH at 7 x 10(-5) M in the medium. Secretory transport was saturated at the same bath PAH concentration in perfused tubules. Urate and PAH transports inhibited each other, thus suggesting a common transport mechanism mainly located in the S2 segment. Probenecid was a strong and PZA a weak inhibitor of this transport system.
Distal tubular function in superficial rat tubules during volume expansion
Authors: Diezi J. , Nenniger M. , Giebisch G.
Published: December 2017

Free-flow micropuncture experiments were carried out on superficial late proximal and distal tubules during hydropenic conditions and during extracellular volume expansion. Fluid collected from tubules was analyzed for inulin and sodium. During volume expansion, renal perfusion pressure to one kidney was reduced so that the increase in distal sodium and fluid delivery that normally occurs after saline loading was prevented. Although urinary sodium excretion remained significantly elevated in such kidneys, the rate of sodium reabsorption along the distal tubules was not different from that occurring under nondiuretic conditions. It is concluded that those factors that reduce net sodium transport in the proximal tubule during extracellular volume expansion do not act on superficial distal tubules. Additional factors beyond the distal tubule contribute to increased sodium excretion and can be shown to be activated even when delivery of fluid and sodium out of superficial distal tubules is normal.