bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation of distal tubular delivery and reabsorptive rate to nephron filtration
Authors: Blantz R. C. , Konnen K. S.
Published: December 2017

The tubuloglomerular feedback hypothesis states that filtration rate in a single nephron unit (SNGFR) is controlled or modified through variations in the rate of either distal delivery or tubular reabsorption in that same nephron. We have reexamined this hypothesis by varying the perfusion rate of the late proximal tubule from normal (10 nl/min) to supranormal values (30 nl/min) in a reversible fashion and measured the resultant nephron filtration rate. Three perfusion fluid were utilized: group I, a solution simulating late proximal tubular fluid (11 mM HCO3); group II, a solution with a higher HCO3 concentration (30 mM HCO3); and group III, a solution simulating early proximal tubular fluid. In group I SNGFR was 27.2 nl/min during perfusion from the late proximal tubule at 10 nl/min and fell to 19.8 nl/min during the 30 nl/min perfusion rate. Group II SNGFR was 27.7 nl/min at the 10 nl/min rate and 19.0 nl/min during the 30 nl/min perfusion. Groups I and II then demonstrated a completely reversible tubuloglomerular feedback response. In group III, the SNGFR at 10 nl/min was 26.2 nl/min and 23.4 nl/min at the 30 nl/min perfusion rate and were significantly different. Evaluation of collections of distal tubule fluid in perfused nephrons revealed that increased absolute reabsorption of water and chloride between late proximal and distal tubules was associated with the reductions in SNGFR in the same nephron. A strong candidate for the afferent limb of this system is the change in absolute chloride reabsorption between late proximal and distal tubules.
Statistical models for renal micropuncture studies
Authors: Raman S. , Mousseau G. , Levine D. Z.
Published: December 2017

Statistical issues relating to data analysis of re-collection micropuncture experiments are presented. In the presence of significant animal-treatment interaction, namely, differential response of each animal at different levels of the treatment, the conventional paired or unpaired t testing would not be entirely appropriate. Accordingly, two analysis of variance (ANOVA) models have been derived for the appropriate paired and unpaired designs of micropuncture experiments. Interactive computer programs have been written for both these analyses, and the results are illustrated with experimental data. An example is presented in which the results are statistically significant with paired t testing and by analysis of variance for unequal number of tubules but not when the animal-treatment interaction is included in the analysis of variance model. To investigate linkage in renal transport mechanisms, we propose the use of partial correlation analysis. Experimental results from our laboratory are used to illustrate these techniques.
Renal excretion of allantoin in rats: a micropuncture and clearance study
Authors: Briggs J. P. , Levitt M. F. , Abramson R. G.
Published: December 2017

Free-flow micropuncture and clearance studies were performed to evaluate the transport of allantoin inthe rat kidney. Inn all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. With a two-step column chromatographic technique, radiolabeled uric acid and allantoin were separated in plasma, urine, and tubular fluid, and the [2-14C]allantoin concentration was determined. Tubular fluid collections were obtained under hydropenic and control coneated animals in the control and volume-expanded states. Clearance data were obtained in oxonic acid-treated animals under the same experimental conditions. These studies indicate that allantoin is not bound to plasma protein and is, therefore, freely filterable. Neither net reabsorption nor net secretion of allantoin was evident along the length of the nephron. The bubular handling of allantoin was demonstrated to be dissociated from that of uric acid in all experimental states. No significant intrarenal production of allantoin from uric acid was observed.
Kinetic analysis of potassium transport in bullfrog kidney
Authors: Sullivan L. P. , Welling D. J. , Deeds D. G. , Simone J. H.
Published: December 2017

Techniques have been developed for studying the distribution and the rates of exchange of K among urine, the tubular cells, and the circulation in the isolated, pump-perfused, bullfrog kidney. Tubular cells were loaded with 42K via the portal circulation, and the subsequent washout of the tracer into the vena cava and into urine was measured. Analysis of the data indicated the existence of at least three cellular pools of K. Pools a and b have half times of exchange of 1.1 and 4.1 min and contain about 25 and 40% of tissue K, respectively. The remainder of cellular K is contained in one or more very slowly exchanging pools. The rate of exchange of K at the basolateral surface of tubular cells is 50-fold greater than at the luminal surface. A pulse-washout method was also devised to permit control and experimental measurements to be made in the same kidney. With this technique, we found that portal perfusion with 10 mM K increased the rate of uptake into pools a and b from the circulation and the rate constants for efflux into the urine from both pools, Acetazolamide increased uptake into pool a and the rate constants for efflux into the urine from both pools.
Sodium retention and ascites formation in dogs with experimental portal cirrhosis
Authors: Levy M.
Published: December 2017

Experimental cirrhosis was produced in dogs by the sporadic feeding of dimethylnitrosamine for the purpose of studying the temporal relationships between urinary sodium retention, plasma volume expansion, and ascites formation. Sodium retention started about 16 days following the onset of cirrhosis and preceded ascites formation by about 10 days. Plasma volume increased by 9% (P less than 0.05) within 3–4 days of sodium retention and expanded further as ascites accumulated. Splanchnic plasma volume was greater by 161 ml in 10 cirrhotic dogs with ascites than in 14 normal dogs. Nonsplanchnic volume was greater by 96 ml (P less than 0.05). Thus, the “effective” as well as the splanchnic component of the vascular space was expanded. Paracentesis did not cause the re-formation of ascites in five dogs as long as dietary salt was denied. Refeeding permitted reaccumulation of ascites and further plasma volume expansion. Renal perfusion remained constant as dogs became progressively cirrhotic. We conclude that ascites formation depends on the prior retention of urinary sodium, and occurs as an “overflow” phenomenon. A contracted effective plasma volume does not appear to be necessary for continuing sodium retention.
Relationship between mineralocorticoids and renal Na+-K+-ATPase: sodium reabsorption
Authors: Westenfelder C. , Arevalo G. J. , Baranowski R. L. , Kurtzman N. A. , Katz A. I.
Published: December 2017

To evaluate the mechanism responsible for the effect of deoxycorticosterone acetate (DOCA) on renal Na+-K+-ATPase, we compared the relative contribution of this hormone and of increased absolute sodium reabsorption (TNa) to the restoration of the enzyme in kidneys of adrenalectomized rats. In study A, adrenalectomized animals maintained on a salt-free diet received 5 mg/kg per day DOCA i.m., while sham-operated and untreated adrenalectomized rats receiving the same diet served as controls. Absolute TNa and Na+-K+-ATPase specific activity in the cortex and outer medulla of DOCA-treated rats were similar to those measured in untreated adrenalectomized animals, but were significantly lower than in sham-operated controls. In study B, the adrenalectomized rats did not receive DOCA but were fed a high salt diet and received isotonic saline, 50 ml/kg per day s.c. Absolute TNa and cortical and medullary Na+-K+-ATPase specific activity were significantly higher in the salt-loaded group than in both adrenalectomized and sham-operated rats deprived of salt. These results suggest that absolute sodium reabsorption is a major determinant of renal Na+-K+-ATPase activity, and that the effect of DOCA on this enzyme is secondary to its stimulation of absolute tubular sodium transport.
The sodium transport pool
Authors: Macknight A. D. , Leaf A.
Published: December 2017

The sodium transport pool in epithelial cells represents sodium involved in active transport across the epithelium. There has been much controversy about the size of such a pool and even about its existence. Techniques for estimating the size of this pool are described. By analysis of toad bladder epithelial cells scraped from hemibladders mounted in chambers under a variety of conditions it has proved possible to detect and to quantify a sodium transport pool. Only about 20 percent of non-inulin space sodium measured flame photometrically is contained in this pool. This represents the total sodium entering cells from the mucosal medium, is in good agreement with the cellular sodium measured by the electron microprobe, and averages some 10-16 mmol/kg tissue H2O. Measurements of the pool in other tissues are considered.
Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade
Authors: Hoffman W. E. , Ganten U. , Phillips M. I. , Schmid P. G. , Schelling P. , Ganten D.
Published: December 2017

The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.
Physical properties of isolated perfused basement membranes from rabbit loop of Henle
Authors: Welling L. W. , Welling D. J.
Published: December 2017

Isolated, perfused segments of late proximal straight tubule, descending thin limb of Henle, and ascending thick limb of Henle from the rabbit were studied before and after removal of the epithelium with sodium deoxycholate. The relationship between transmural hydrostatic pressure and outer tubule diameter was similar in paired intact tubules and basement membranes, indicating that basement membrane is the principal determinent of tubule distensibility. As calculated from teh measured perfusate flow at several different transmembrane hydrostatic pressures, the hydraulic conductivity of the basement membranes was 6-8 X 10(-3) cm3/cm2.min.cmH2O. With use of these LP values and the calculated oncotic pressure required experimentally to reduce transmembrane hydrostatic pressure transiently to zero, the apparent reflection coefficient of the basement membranes for serum albumin was estimated to be 0.05-0.16. It is concluded that basement membranes of the loop and of other previously studied segments of rabbit nephron provide very strong and elastic mechanical support to the epithelium while having minimal resistance to flow of water and of solutes as large as serum albumin.
Fluid absorption with and without sodium in isolated perfused snake proximal tubules
Authors: Dantzler W. H. , Bentley S. K.
Published: December 2017

Net fluid absorption (JV) was studied in isolated, perfused snake (Thamnophis spp.) proximal renal tubules. With standard (150 mmol/liter Na+) bicarbonate-buffered Ringer in perfusate and standard Ringer plus dextran (4 g/100 ml) in bath, JV was about 0.9 nl min-1 mm-1. Removing dextran from bath reduced JV by about 20 percent. When sodium in perfusate was replaced with choline JV approached zero. However, when sodium in bath as well as perfusate was replaced with choline, JV returned to control level. Results were the same when sodium was replaced with tetramethyl-ammonium, sodium chloride was replaced with sucrose or lactose, or chloride was replaced with methyl sulfate. In contrast, replacing sodium in perfusate or in both perfusate and bath with lithium did not reduce JV. Fluid absorption was always isosmotic. Replacing bicarbonate with phosphate or Tris in sodium-containing media had no effect on JV, but the presence of buffer in sodium-free or low-chloride media may have been important for JV. Reducing temperature 10 degrees C reduced JV by about 35 percent with either sodium chloride or sucrose in both perfusate and bath. The results indicate that isosmotic fluid absorption can occur when lithium is substituted for sodium or when some other substitution is made for sodium, chloride, or both in perfusate and bath simultaneously.
Effects of prolonged vasopressin treatment in Brattleboro rats with diabetes insipidus
Authors: Mohring J. , Kohrs G. , Mohring B. , Petri M. , Homsy E. , Haack D.
Published: December 2017

Normal Long-Evans rats (LE) exhibited diurnal variations of plasma arginine vasopressin (AVP) concentrations with peak values at 10 A.M. and minimum values at 1 P.M. Brattleboro rats heterozygous for hypothalamic diabetes insipidus (DI) had significantly reduced plasma AVP concentrations and increased plasma osmolalities when compared with LE rats. By prolonged injection of 100 mU/day of vasopressin tannate (VPT) into Brattleboro rats homozygous for DI, plasma AVP concentrations close to those of LE rats were achieved. Potassium was retained for 7 days until escape of vasopressin-induced potassium retention occurred. When 500 mU VPT were injected into DI rats, high plasma AVP levels were induced. Potassium was retained for 2-3 days. After initial sodium retention, periods of natriuresis occurred. During treatment with 100 mU VPT/day most of the alterations present in DI rats were corrected, which included increased water turnover and external water loss, increased hematocrit and plasma sodium concentrations (but not increased plasma osmolalities), hypokalemia, increased activity of the renin-angiotensin system, and reduced adrenocortical function.
Mechanism of the glucocorticoid-induced increase in glomerular filtration rate
Authors: Baylis C. , Brenner B. M.
Published: December 2017

In order to investigate the mechanism(s) by which glucocorticoids increase GFR the determinants of glomerular ultrafiltration were measured in two groups of seven Munich-Wistar rats. Group 1 rats were normal controls and group 2 rats were pretreated with methylprednisolone (MP), 15 mg/kg per day for 4 days prior to study. In rats given MP mean values for SNGFR were about 25% higher than in the control group, averaging 33.6 +/- 1.6 (SE) vs. 27.0 +/- 1.0 nl/min. Mean values for initial glomerular plasma flow rate (QA) were also about 25% higher in MP-treated rats, averaging 83.4 +/- 3.9 vs. 65.9 +/- 1.9 nl/min in controls. Mean values of the transglomerular hydraulic pressure difference (deltaP) as well as afferent (IIA) and efferent (IIE) oncotic pressures were essentially similar between control and MP-treated rats. Filtration pressure equilibrium, i.e., equality between IIE and deltaP, obtained in both groups and the mean minimum estimates of the ultrafiltration coefficient (Kf) were also similar between control and MP-treated rats. Thus, the rise in SNGFR following MP is entirely due to the increase in AQ, rather than to changes in the other determinants of ultrafiltration.
Superficial nephron tubular-vascular relationships in the rat kidney
Authors: Weinstein S. W. , Szyjewicz J.
Published: December 2017

Silicone rubber injections of methyl salicylate-cleared rat kidneys were performed. In 50 of 56 injections of superficial nephrons with their accompanying blood supply, the efferent vessel and early proximal tubule were closely approximated. In 18 of 21 tubular injections filling through the pars recta, the proximal tubule folded upon itself with early and late proximal segments, in close contact, located over their parent glomerulus, and the midproximal segments separate and located over their parent interlobular artery. The distribution of blood was serially through the early-late proximal region above the glomerulus via a long unbranched efferent vessel, via branches over the capsular surface, via capillaries down through the midproximal region, then into the interlobular vein. The observed anatomical pattern of the superficial nephron appears to permit direct functional interactions between the juxtaposed early and late proximal tubule, and in turn may effect midproximal function via the distribution of blood (modified by early proximal) from the efferent vessel to midproximal convolutions. In addition, the relationship between specific segments of the proximal tubule and specific portions of the postglomerular peritubular blood supply may be important in determining the distribution of peritubular physical forces to these nephrons.
Mathematical modeling of transport in structured tissues: corneal epithelium
Authors: Friedman M. H.
Published: December 2017

A computer model has been constructed to describe multi-ionic transport across an epithelium consisting of a transcellular pathway in parallel with a shunt. The model is parameterized to simulate rabbit corneal epithelium. Calculations show that when this tissue is stimulated by epinephrine at open circuit, there is a flux of electrolyte across it into the tears. The magnitude of the flux is sensitive to paracellular resistance, which also affects the potentials across the mucosal cell border and entire epithelium. The electrolyte extrusion rate of the tissue is found to be near zero in the absence of stimulation. More generally, it is shown that for epithelia whose structure is at least as complex as that used here, the active transport rate of ions exceeds their net flux at short circuit; tracer fluxes in one direction at two polarizations cannot be used to identify active transport or significant tracer interactions; and tracer measurements yield ionic permeabilities only at short circuit and only if the ion is not actively transported.
Selective effects of bumetanide on chloride transport in bullfrog cornea
Authors: Candia O. A. , Schoen H. F.
Published: December 2017

Frog corneas were mounted in a modified Ussing chamber and short-circuit current (SCC) and unidirectional Cl fluxes were measured. Bumetanide, a loop diuretic, at concentrations as low as 10(-7) M, reduced the SCC 29%. At 10(-5) M, bumetanide reduced the SCC 96% and increased transcorneal electrical resistance 20-51%. The forward Cl flux declined from 0.71 +/- 0.04 to 0.20 +/- 0.03 mueq/h.cm2 (n, 7), while, in separate experiments, the backward Cl flux did not change significantly (from 0.22 +/- 0.03 to 0.23 +/- 0.04; n, 7). When corneas were mounted in Cl-free Ringer and the net Na transport was stimulated with amphotericin B, 10(-5) M bumetanide had no effect on the SCC. In separate experiments the effect of 10(-5) M bumetanide on the O2 consumption was measured in a stirrer bath assembly. Bumetanide decreased the O2 consumption from 352 +/- 14 to 297 +/- 19 microliter/h.cm2 (significantly different from sham-treated controls). This decrease was similar to that obtained with furosemide or when Cl was removed from the bathing medium. We infer from these results that bumetanide is a selective inhibitor of active Cl transport in the bullfrog cornea.
Effect of SITS on organic anion transport in the rabbit kidney cortical slice
Authors: Hong S. K. , Goldinger J. M. , Song Y. K. , Koschier F. J. , Lee S. H.
Published: December 2017

The effect of SITS (4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene) on the transport of organic ions in the rabbit kidney cortical slice was studied. SITS at a concentration of 10(-4) to 10(-3) M significantly decreased the slice-to-medium (S/M) concentration ratio of the organic anions p-aminohippurate (PAH), and 2,4,5-trichlorophenoxyacetate, but had no significant effect on that of the organic cation tetraethylammonium. The S/M ratio of PAH decreased to 0.52 +/- 0.03 (SE) in the presence of 10(-3) M SITS. The inhibition of PAH uptake caused by SITS was reversed in the presence of 0.5% bovine serum albumin in the medium. SITS at a concentration of 10(-4) M had no significant effect on the efflux of PAH. However, there was a small increase in PAH efflux at a concentration of 10(-3) M SITS. A Lineweaver-Burk analysis of the data indicates that SITS competitively inhibits PAH uptake and that SITS has a Ki value of 2.3 X 10(-4) M. SITS had no effect on the tissue water content, [14C]inulin space, or intracellular Na and K concentrations. It is suggested that the primary effect of SITS is to inhibit the entry of organic anions from the medium into the cell across the basolateral membrane.
Apparent escape rate of RIHSA and 51Cr-labeled erythrocytes from the blood of volume-expanded rats
Authors: Ackermann U.
Published: December 2017

The disappearance rate constant of radioiodinated human serum albumin (RIHSA) and 51Cr-tagged erythrocytes was measured in rats before and after intravenous, isoncotic blood volume expansion (6% bovine albumin; 75 or 33% of blood volume). Before volume expansion the average slope of the semilogarithmically plotted plasma RIHSA activity was -2.068 X 10(-3) +/- 0.146 X 10(-3) (SE) min-1. The slope was not significantly changed when tested by subsequent tracer injections which were made immediately after and 1 h after volume expansion. Preinfusion plasma volume (PV) was constant, but total erythrocyte volume (RCV) increased at a significant rate from 0.0253 +/- 0.0030 to 0.0300 +/- 0.0038 ml/g body wt over the 2-h period. PV was elevated and RCV was unchanged by the infusion, but both decreased significantly thereafter. The observed erythrocyte loss could not be accounted for by sampling or bleeding. Arterial hematocrit remained constant while RCV and PV were decreasing, and it was identical to whole-body hematocrit throughout. It was concluded that 1) isoncotic albumin expansion did not change the rate constant of transcapillary albumin loss; 2) nonsteady state PV could be calculated from a single preinfusion RIHSA dose; and 3) sequestration of blood may be a part of the rat's response to volume expansion.
Mobilization of ascites in cirrhotic dogs following furosemide or mannitol diuresis
Authors: Levy M. , Richard C.
Published: December 2017

Mobilization of ascites was studied in 20 anesthetized dogs with experimental cirrhosis following a mannitol- or furosemide-induced diuresis. Observations were made at 2 h following the drug, at which time the diuresis was invariably completed, and repeated at 4 h following a 2-h recovery period, during which the ureters were clamped to prevent further urinary losses. In the furosemide group the mean urinary loss was 459 +/- 6 ml and was accompanied by a decline in central venous pressure and hemoconcentration. At 2 h plasma volume had declined by 14% from control values, but at 4 h plasma replenishment was 99% complete. At this time ascites volume had decreased by 467 ml, acting as the major source for vascular replenishment. In the mannitol group, the average urinary loss was 190 +/- 10 ml and was accompanied by maintenance of venous pressure, lack of hemoconcentration, and hyponatremia. At 2 h plasma volume had expanded from control values by 22%, but at 4 h vascular replenishment was only 78% complete. The average ascites volume had decreased by only 55% of the diuretic loss, and was mobilized by a complex sequence of events involving movement of intracellular water.
Cardiovascular responses to blockade of angiotensin and alpha-adrenergic receptors
Authors: Borucki L. J. , Levenson D. , Hollenberg N. K.
Published: December 2017

Both angiotensin and alpha-adrenergic blocking agents reduce arterial blood pressure in hypovolemic states. We have compared the effects of an angiotensin antagonist (saralasin) and an alpha-adrenergic blocking agent (phenoxybenzamine) in supramaximal dosage on cardiac output, total peripheral resistance, and venous tone in rabbits rendered hypovolemic by restriction of sodium intake, supplemented by a furosemide-induced diuresis 48 h prior to study. Saralasin (10 microgram/kg per min) reduced arterial blood pressure significantly (-15 +/- 1.2 mmHg) despite an unchanged cardiac output (P less than 0.025) due to a fall in total peripheral resistance. Phenoxybenzamine (5 mg/kg) induced a much larger fall in arterial blood pressure (-28 +/- 3.6 mmHg), despite an identical reduction in total peripheral resistance, because cardiac output also fell (+/- 9 ml/kg per min). The reduction in cardiac output was associated with a significant increase in hindlimb venous distensibility (P less than 0.001) after alpha-adrenergic blockade. Saralasin, conversely, had no influence on venous tone. Adrenergic mechanisms contribute to cardiovascular homeostasis through an influence on both arteriolar and venous tone, whereas the effect of angiotensin is directed entirely to the arteriolar side of the circulation.
Characterization of distal hydrogen ion secretion in acute respiratory alkalosis
Authors: Sehy J. T. , Roseman M. K. , Arruda J. A. , Kurtzman N. A.
Published: December 2017

The effect of acute respiratory alkalosis (ARA) on distal nephron H+ secretion was evaluated by measuring urine-to-blood (U-B) Pco2 in dogs with highly alkaline urine (urine pH greater than 7.8). ARA led to a significant decrease in U-B Pco2 and in urine HCO3 concentration; urine pH, however, increased significantly, indicating that the decrease in urine Pco2 was of greater magnitude than the decrease in urine HCO3 concentration. For any given urine HCO3 concentration urine Pco2 was lower (i.e., urine pH was higher) in ARA than in controls. Administration of tris(hydroxymethyl)aminomethane (Tris) during ARA resulted in a significant increase in U-B Pco2 to control values. In animals with moderately alkaline urine (urine pH 6.4--7.4) and high urine PO4 concentration, ARA resulted in a significant decrease in UB-Pco2 and urine PO4 concentrations. Neutral PO4 infusion in these dogs resulted in an increase in urine PO4 concentration and U-B Pco2 to control levels. These data demonstrate that ARA results in a significant decrease in U-B Pco2 that is not solely attributable to changes in urine HCO3 concentration. The observation that Tris and PO4 infusion during ARA raises U-B Pco2 to control levels suggests that the ability to secrete H+ is intact.
Distribution along the rat nephron of three enzymes of gluconeogenesis in acidosis and starvation
Authors: Burch H. B. , Narins R. G. , Chu C. , Fagioli S. , Choi S. , McCarthy W. , Lowry O. H.
Published: December 2017

Methods were devised or modified which made it possible to measure phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase in seven defined parts of single nephrons and in patches from thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. All three enzymes were essentially confined to the proximal tubule. In normal kidneys, the levels were highest in the proximal convoluted tubule. Glucose-6-phosphatase was 20 times higher in the early part of the convoluted segment than in the late part of the straight segment. With one exception, in acidosis, only phosphoenolpyruvate carboxykinase increased (fourfold in the proximal convoluted segment but much less in the straight portion). In starvation, phosphoenolpyruvate carboxykinase increased about as much as in acidosis in the proximal straight tubule, but not as much in convoluted portions, whereas glucose-6-phosphatase rose modestly in both parts of the proximal tubule and fructose bisphosphatase rose only in the straight tubule, especially the early segment. It is suggested that ammoniagenesis can accompany gluconeogenesis in the proximal convoluted tubule but not in the straight segment.
Characterization of the postocclusive response of renal blood flow in the cat
Authors: Spielman W. S. , Osswald H.
Published: December 2017

In contrast to the postocclusive hyperemia of brain, heart, and skeletal muscle, the hemodynamic response of the kidney following renal artery occlusion is highly variable in that both hyperemia and ischemia have been reported. The present study evaluates the factors influencing the renal response to complete renal artery occlusion (5-60 s) in the anesthetized cat. Marked postocclusive vasoconstriction could only be domonstrated in meclofenamate-treated (10 mg/kg) cats. The delta% renal blood flow (RBF) (30-s occlusion) was 16 +/- 4 in controls and 54 +/- 4 after meclofenamate (n= 10; P less than 0.001). Chronic denervation of the kidney, alpha-adrenergic receptor blockade, or infusion of [Sar1, Ile8]angiotensin II(2 microgram/min per kg) did not affect the postocclusive reduction of RBF, indicating that the vasoconstriction was independent of renal nerves, catecholamines, and circulating angiotesin II. Adenosine injected into the renal artery of five cats caused a dose-dependent transient fall of RBF. A dose of 100 nmol adenosine reduced RBF by 44 +/- 6% whereas after meclofenamate only 1 nmol produced the same degree of vasoconstriction. In summary, this study demonstrates a marked potentiation of the postocclusive vasoconstrictor response and the vasoconstrictive action of adenosine by meclofenamate in the anesthetized animal. No evidence was obtained to support a role for the sympathetic nervous system or circulating angiotensin II in mediating the postocclusive vasoconstriction.
Carbonic anhydrase in the generation of cochlear potentials
Authors: Prazma J.
Published: December 2017

The experiments on 18 guinea pigs were divided into two groups and each group was arranged in such a way that the effect of hypercapnia (generated by breathing 10% CO2-90% O2) was investigated with and without inhibition of carbonic anhydrase by methazolamide, 25 mg/kg, in the first group and acetazolamide, 50 mg/kg, in the second group, administered intravenously. The endocochlear potentials (EP) and endocochlear PO2 were recorded by microelectrodes introduced into the scala media, and cochlear microphonics (CM) were monitored by a silver-wire electrode from the round window. In the first exposure to hypercapnia (20-40 min) EP increased about + 6 mV. At the same time CM decreased; the reason for this is not yet known. During the second period of hypercapnia (80-100 min) when carbonic anhydrase was inhibited with methazolamide and acetazolamide, EP did not elevate as during the first period when carbonic anhydrase was not inhibited. In this work, under specific conditions, it was observed for the first time that carbonic anhydrase affects the generation of EP.
Uncoupling of proximal sodium bicarbonate from sodium phosphate transport by bumetanide
Authors: Puschett J. B. , Sylk D. , Teredesai P. R.
Published: December 2017

Re-collection micropuncture of late proximal tubular segments and simultaneous clearance studies were performed in chronically thyroparathyroidectomized dogs before and after the intravenous administration of bumetanide. The drug, a new sulfonamide-derivative diuretic, inhibited proximal fractional sodium and fluid transport by 0.12 (from 0.44 +/- 0.04 to 0.32 +/- 0.04, P less than 0.05) and that of bicarbonate by 0.14 (from 0.43 +/- 0.05 to 0.29 +/- 0.07, P less than 0.02). Tubular fluid bicarbonate concentration was unchanged, indicating a reduction in the transport of this ion proportionate to that of tubular fluid. However, unlike sodium and bicarbonate reabsorption, fractional proximal phosphate transport was unaltered (from 0.65 +/- 0.04 to 0.62 +/- 0.04, P greater than 0.40). The drug induced a substantial natriuresis; the percentage of filtered sodium excreted rose from 0.4 +/- 0.1 to 13.1 +/- 2.4% (P less than 0.005). Bicarbonate and phosphate excretion rose more modestly: the percentage excretion of the former ion increased from 0.9 +/- 0.3 to 3.7 +/- 0.08% (P less than 0.005) and that for phosphate doubled (from 3.4 +/- 1.0 to 6.8 +/- 1.3%, P less than 0.025). However, urinary pH did not change. Accordingly, bumetanide uncoupled the transport of sodium bicarbonate from that of sodium phosphate in the proximal convoluted tubule. It is concluded from these data that the action of bumetanide in the proximal convoluted tubule is probably not related either to carbonic anhydrase inhibition or to the impairment of sodium-phosphate-linked transport.
Stimulation of adenylate cyclase in isolated rat glomeruli by prostaglandins
Authors: Schlondorff D. , Yoo P. , Alpert B. E.
Published: December 2017

The effect of prostaglandins and various agents on cyclic adenosine 3',5'-monophosphate generation was studied in isolated rat glomeruli. Specific activity of adenylate cyclase in the glomeruli showed a 12-fold increase over the crude homogenate and a fivefold increase over a tubular preparation. Prostacyclin (PGI2) preferentially stimulated adenylate cyclase of isolated glomeruli at a concentration as low as 10(-9) M. Prostaglandins (PGE1, PGE2, and PGA2) and parathyroid hormone (1–34 synthetic PTH fragment) increased adenylate cyclase in glomeruli with maximal stimulation at 2 X 10(-5) M and 2–4 microgram/ml, respectively. No inhibition of PGE2 on PTH stimulation was observed. Isoproterenol (2 X 10(-4) M) caused a small stimulation, while PGF2alpha, arginine vasopressin, and angiotensin II were ineffective. The presence of guanosine triphosphate in the adenylate cyclase assay enhanced basal and PGE2- and PTH-stimulated activity, but had no effect on NaF stimulation. These findings show an effect of prostaglandins and PTH on the glomerular cAMP system and raise the possibility of a physiological action of these agents on the glomerulus.
Organic acid secretory pathway and urinary excretion of prostaglandin E in the dog
Authors: Rosenblatt S. G. , Patak R. V. , Lifschitz M. D.
Published: December 2017

Urinary prostaglandin E (PGE) has been utilized as an index of renal PGE production. Recent studies, however, have suggested that the organic acid secretory pathway is a major determinant of endogenous UPGEV (urinary excretion of PGE). The following experiments were designed to quantitatively test this latter view. In clearance studies the administration of para-aminohippurate (PAH) or probenecid (25 mg/kg) failed to alter endogenous UPGEV although PAH clearance fell with probenecid. Comparison of the excretion patterns of exogenously administered [3H]PGE and [14C]inulin after intra-arterial injection into the dog renal artery (Chinard technique) demonstrated both glomerular filtration and secretion of [3H]PGE. Blockade of the organic acid pathway by probenecid (25 mg/kg) abolished [3H]PGE secretion. Indomethacin (1 mg/kg) did not alter the secretion pattern of [3H]PGE, but decreased endogenous UPGEV by over 80%. Because this low dose of indomethacin did not decrease [3H]PGE secretion, it probably decreased endogenous UPGEV by inhibiting synthesis. Thus, these tracer studies do indeed confirm the suggestion that PGE may be excreted by the organic acid pathway. However, the failure of total endogenous UPGEV to fall after blockade of the organic acid pathway would suggest that the component of UPGEV due to this mechanism is quantitatively insignificant.
Dual effects of amphotericin B on ion permeation in toad urinary bladder epithelium
Authors: Reuss L. , Gatzy J. T. , Finn A. L.
Published: December 2017

The mechanisms of action of amphotericin B on the electrical properties of the toad urinary bladder epithelium were studied with microelectrode techniques. Cell membrane and transepithelial electrical potentials and resistances were measured in the absence and in the presence of the drug during exposure to bathing mediums of different ionic compositions. As observed previously by other investigators, amphotericin B produces a dramatic decrease of transepithelial electrical resistance (Rt) and an increase of the rate of sodium transport. Our results indicate that the effect of the drug on Rt depends in part on an increase in Na conductance across the luminal cell membrane (amiloride-insensitive), but is caused mainly by an increase of ionic conductances (with the sequence GK greater than GNa greater than G choline greater than GCI) at a site in parallel with the impaled cells (i.e., across a cell type not investigated by the microelectrode measurements or across the paracellular pathway.
Interactions between volume expansion or diuretics and compensatory adaptation
Authors: Arslan Y. , Diezi J. , Peters G.
Published: December 2017

Glomerular filtration rate, urine flow, and Na excretion were measured 3– –4 h after unilateral nephrectomy (1/2Nex) or sham operation in unanesthetized rats infused with isotonic saline (0.05––0.75 ml/min) and additionally injected with acetazolamind (20 mg/kg i.p.) or furosemide (5 mg/kg i.p., or 0.2 mg/kg i.v., or 2.0 mg/kg i.v.) or with both agents. Glomerular filtration rate of unilaterally nephrectomized rats averaged 50% of controls. Under all experimental conditions investigated, absolute water and Na excretions were similar in 1/2Nex and sham-operated rats. The fractional excretion (FE) of water and Na was increased 1.5- to 2.2-fold in 1/2Nex animals. The diuretic effects of volume expansion, of the two diuretic agents, and of contralateral nephrectomy consistently were additive. The “compensatory” increase of FESa following contralateral nephrectomy entailed a proportional increase of the diuretic effects of agents given subsequently. Urinary furosemide excretion 15 min after intravenous injection in unilaterally nephrectomized rats was smaller than in controls. The additivity of the diuretic effects of contralateral nephrectomy (“compensatory adaptation”) and volume expansion and/or diuretic agents appears to be partly explained by different sites of action.
Actions of adrenergic agonists on isolated excretory ducts of submandibular glands
Authors: Denniss A. R. , Schneyer L. H. , Sucanthapree C. , Young J. A.
Published: December 2017

The effects of norepinephrine and isoproterenol on the transepithelial potential difference (PD) and the net transepithelial fluxes of Na, K, Cl, and HCO3 of the main ducts of the submandibular glands of rats and rabbits have been studied by microperfusion of ducts incubated in vitro in an artifical bathing medium. In the rabbit duct, both catecholamines caused depolarization and reduced transepithelial Na reabsorption at concentrations above 10(-29) M. In the rat duct, norepinephrine reduced PD and net Na reabsorption and, in addition, inhibited net K secretion at concentrations of 10(-7) M and above. Isoproterenol also depolarized the duct and reduced net K reabsorption, but at concentrations of 10(-9) M it stimulated net Na reabsorption, whereas at concentrations of 10(-4) M it inhibited Na reabsorption. The stimulation caused by isoproterenol at low concentrations could be blocked by prior administration of propranolol. The results suggest that electrolyte transport, by both rat and rabbit ducts, may be influenced not only by sympathetic nerve activity but also by physiological changes in the concentrations of circulating catecholamines. Inconsistencies in the literature regarding the sensitivity of the rabbit duct to catecholamines and the response of the rat duct to isoproterenol have now been resolved.
Relative sodium-to-chloride permeability in the proximal convoluted tubule
Authors: Berry C. A. , Rector F. C.
Published: December 2017

Electrophysiological techniques were used in isolated perfused proximal convoluted tubules (PCT) to examine the effect of changes in bath protein concentration on paracellular properties and of active salt transport on relative sodium-to-chloride permeability (PNa/PCl). Control transepithelial potential difference (PD) and NaCl dilution potentials were determined in tubules perfused and bathed with an ultrafiltrate-like solution. PNa/PCl was calculated from the NaCl dilution potential. In the first series of experiments PD and PNa/PCl were redetermined in the same PCT following three experimental maneuvers known to inhibit active salt transport. Addition of 10(-5) M ouabain to the bath, removal of luminal glucose and alanine, and removal of luminal glucose, alanine, bicarbonate, and acetate reduced PD but did not alter the NaCl dilution potential, and therefore PNa/PCl was constant. Constant PNa/PCl in these experiments suggests a) that lowering bath NaCl concentration does not change transcellular current flow, b) that PNa/PCl reflects the ion selectivity of the paracellular pathway, and c) that the ion selectivity of the paracellular pathway is independent of active salt transport. In the second set of experiments PD and PNA/PCl were redetermined following addition of protein to the bath. Neither PD nor PNa/PCl was altered. Analyses of these data argue against modulation of paracellular permeability by bath protein in the in vitro rabbit PCT and suggest that the ion selectivity of the paracellular pathway is determined predominantly by junctional complexes rather than lateral intercellular spaces.
Effect of adrenal steroids on vasopressin-stimulated PGE synthesis and water flow
Authors: Zusman R. M. , Keiser H. R. , Handler J. S.
Published: December 2017

Page F532: R. M. Zusman, H. R. Keiser, and J. S. Handler. “Effect of adrenal steroids on vasopressin-stimulated PGE synthesis and water flow.” Page F536: The illustration in Figure 3 should have appeared as Figure 4. The illustration in Figure 4 should have appeared as Figure 3.
Time course of the renal response to triiodothyronine in the rat
Authors: Lo C. S. , Lo T. N.
Published: December 2017

Experiments were carried out to compare temporal changes in glomerular filtration rate (GFR), filtered Na+ load, and renal cortical (Na+ + K+)-adenosine triphosphatase (Na-K-ATPase) activity in the hypothyroid rat after administration of a single dose of triiodothyronine (T3) (50 microgram/100 g body wt). The cortex showed an increase in Na-K-ATPase at 24 h and progressive increases to a peak of 62% at 48 h. GFR and filtered Na+ load showed no changes at 24 and 48 h. At 72h, however, significant increases of 62 and 63% (per rat) were observed in GFR and filtered Na+ load, respectively. The results show that the early increase in Na-K-ATPase activity upon T3 treatment precedes the increases in GFR and filtered Na+ load, suggesting a direct effect of T3 on the regulation of Na-K-ATPase activity in the hypothyroid rat kidney cortex, rather than a secondary response to a primary increase in filtered Na+ load as proposed previously.
Flow dependence of nonelectrolyte absorption in the nephron
Authors: Barfuss D. W. , Schafer J. A.
Published: December 2017

The axial flow dependence of nonelectrolyte absorption was examined in terms of a model incorporating interactions between net volume absorption and both saturable and nonsaturable solute absorption. The model solutions demonstrated that changes in transepithelial solute transport are produced by changes in the average luminal solute concentration. Even passive non-saturable solute absorption was shown to exhibit dependence on the perfusion rate, and, therefore, on the solute delivery rate, which could be incorrectly interpreted as demonstrating the presence of a saturable absorptive mechanism. For a unidirectional lumen-to-bath solute flux mediated in part by a saturable mechanism, the observed flux is dependent on the permeability of any parallel nonsaturable permeation pathway. This permeability also sets a lower bound on the luminal solute concentration which may be achieved during active net solute absorption by determining the rate of passive solute backleak. Extension of the model to incorporate dependence of net volume absorption on the delivery of nonelectrolytes predicted a relationship between perfusion rate and net volume absorption equivalent to approximately one-third of complete glomerulotubular balance.
Coupling of NaHCO3 and NaCl reabsorption in dog kidneys during changes in plasma PCO2
Authors: Mathisen O. , Monclair T. , Raeder M. , Kiil F.
Published: December 2017

To study the relationship between proximal tubular reabsorption of bicarbonate, sodium, and chloride, the effects of changes in plasma PCO2 were examined in anesthetized dogs. Distal tubular reabsorption was inhibited by ethacrynic acid; plasma bicarbonate concentration was kept constant at 33.4 +/- 0.3 mM; glomerular filtration rate (GFR) was varied over a wide range to examine glomerulotubular balance (constant fractional reabsorption). Hypercapnia (PCO2, 112.0 +/- 2.5 mmHg) increased bicarbonate reabsorption by about 30%, and hypocapnia (PCO2, 19.8 +/- 0.6 mmHg) decreased reabsorption of bicarbonate by more than 50% and altered reabsorption of sodium, chloride, and bicarbonate in the molar ratios 2.7:1.6:1, respectively. During hypercapnia the range of glomerulotubular balance was extended to a GFR 125% of control. During hypocapnia glomerulotubular balance was present only at GFR below 50% of control; reabsorption of bicarbonate sodium, and chloride was constant at GFR exceeding 50% of control. During metabolic acidosis hypercapnia had no significant effect on reabsorption of bicarbonate, sodium, and chloride. These observations support the hypothesis that bicarbonate reabsorption is the main driving force for osmotic reabsorption of water and NaCl in the proximal tubules.
Effect of parathyroid hormone on plasma renin activity and sodium excretion
Authors: Smith J. M. , Mouw D. R. , Vander A. J.
Published: December 2017

The interaction between parathyroid hormone (PTH) and the renin-angiotensin system was evaluated in pentobarbital-anesthetized dogs. An intravenous infusion of bovine PTH (1-34) for 1 h was accompanied by a 57% increase (13.7-21.6 ng/ml per h) in plasma renin activity (PRA) which returned toward control levels during the recovery period. Sodium and phosphate excretion also increased. Second the endogenous secretion of PTH was stimulated by infusion of citrate into the blood supply of the thyroparathyroid glands to determine if the stimulatory effect on renin occurred with endogenous secretion of PTH. Phosphate excretion increased, which confirmed PTH secretion. There was a significant rise (57%) in both PRA (6.1-9.8 ng/ml per h) and sodium excretion, the magnitude of the sodium response modulating the increase in PRA. Blood pressure remained constant. In a third set of experiments, thyrocalcitonin was infused intravenously and had no effect on PRA. These data indicate that both exogenous and endogenous PTH can elevate PRA and increase sodium excretion. The sodium effect is probably the result of inhibition of proximal sodium reabsorption by PTH. The mechanism by which PTH elevates PRA is not known.
Effect of adrenal arterial infusion of P-113 on aldosterone secretion in Na-deficient sheep
Authors: Blair-West J. R. , Coghlan J. P. , Denton D. A. , Hardy K. J. , Scoggins B. A. , Wright R. D.
Published: December 2017

To examine the role of the renin-angiotensin system in aldosterone regulation, P-113 ([Sar1,Ala8]angiotensin II) was infused into the arterial blood supply of the transplanted adrenal gland in conscious sheep. Effects on the aldosterone response to infused angiotensin II and III in sodium-replete sheep were compared with effects of P-113 on aldosterone secretion in sodium deficiency. P-113 infusion up to 1,000 microgram/h for 1-2 h did not consistently alter aldosterone secretion in sodium-deficient sheep. However, in sodium-replete sheep P-113 infusion for 20 min at 10 microgram/h or more abolished aldosterone responses to high blood levels of angiotensin II and III produced by systemic intravenous or adrenal intra-arterial infusion. P-113 infusions alone had minor agonist activity on aldosterone secretion in sodium-replete sheep. These results indicate that the increased secretion of aldosterone in Na-depleted sheep is not simply and commensurately determined by increase of angiotensin II and III concentration in the arterial blood perfusing the adrenal gland.