bluuebunny/crossref_metadata_2025 huggingface dataset:
Regeneration of the renal brush border after renal ischemia in rats
Authors: Paddock J. K. , Lada W. , Lowenstein L. M.
Published: December 2017

An early change following mild renal ischemia is the loss of the renal microvilli, which then regenerate morphologically within 6 h. We studied microvillar regeneration in rats with 25 min of renal artery occlusion and subsequent reflow. At subsequent intervals the rats were injected intraperitoneally with [14C]choline and [3H]leucine; 25 min later they were killed and their renal brush border membranes isolated. At 30 min of reflow of blood there was a 77% reduction in the incorporation of [3H]leucine into microvillar protein compared with that of the opposite control kidney (P less than 0.02). The incorporation rose to normal within 60 min. At 30 min of reflow, the incorporation of [14C]choline into phospholipids increased twofold (P less than 0.005), then returned toward normal values after 2 h. The altered incorporation of tracers was not due to change in membrane turnover or substrate pools. The activities of alkaline phosphatase, gamma-glutamyl transpeptidase, and alpha-glucosidase decreased 50% following ischemia (P less than 0.02) and returned to control values within 2 h. Thus, renal damage severe enough to partly efface microvilli is repaired metabolically within several hours.
Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation
Authors: Hostetter T. H. , Olson J. L. , Rennke H. G. , Venkatachalam M. A. , Brenner B. M.
Published: December 2017

Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.
Determinants of the glomerular filtration of proteins
Authors: Deen W. M. , Satvat B.
Published: December 2017

We showed previously that a theoretical model treating the glomerular capillary wall as a membrane with uniformly distributed fixed negative charges can account for the observed filtration rates of charged derivatives of dextran in the rat. Using measurements of electrophoretic mobility to estimate effective molecular charge, a necessary input parameter, we present evidence that this model is also consistent with reported filtration rates of several proteins in the rat. Apparent fixed-charge concentrations calculated for serum albumin and three forms of horseradish peroxidase are in the range of 100-130 meq/liter, comparable to the 120-170 meq/liter obtained for charged dextrans. Theoretical effects of hemodynamic changes on filtration of charged macromolecules are considered. With increases in glomerular plasma flow rate (QA) or transcapillary hydraulic pressure difference (delta P), the filtrate-to-plasma concentration ratio (theta) is generally predicted to decrease for neutral or anionic macromolecules but to increase for cationic substances. The more highly charged the macromolecule (cationic or anionic), the more sensitive theta is to such hemodynamic perturbations. For serum albumin, absolute filtration rates are predicted to increase as much as twofold for moderate decreases in QA combined with increases in delta P. Alterations in protein molecular charge offer an attractive explanation for changes in protein filtration during acidosis or alkalosis.
Cisplatin nephrotoxicity in rats: defect in papillary hypertonicity
Authors: Safirstein R. , Miller P. , Dikman S. , Lyman N. , Shapiro C.
Published: December 2017

We examined the effects of cisplatin (5 mg/kg BW) on renal function in rats. Three days after administration of cisplatin whole kidney clearance of inulin fell and 24-h urine volume increased. Maximal urine osmolality and papillary solute content were reduced. Superficial nephron glomerular filtration rate measured along the proximal tubule, where no leak of inulin could be demonstrated, was reduced in cisplatin-treated animals. Differences between superficial nephron glomerular filtration rate determined in proximal and distal tubules were greater in cisplatin-treated rats than in control rats. Neither a change in fluid or sodium movement along superficial nephrons nor a reduced early distal tubule transepithelial sodium gradient explain the polyuria. Urea was reabsorbed from, not added to, the loop fluid in cisplatin-treated animals. Morphologic changes were evident in the S3 segment of the proximal tubule in cisplatin-treated animals but the glomeruli were normal. Polyuria occurred despite diminished glomerular filtration rate in cisplatin nephrotoxicity. The diminished concentration of salt and urea in the papilla as a result of abnormal function of the collecting duct or pars recta portion of the proximal tubule contributed to the defect in concentrating ability.
Filtration pressure equilibrium: a statistical analysis
Authors: Oken D. E. , Choi S. C.
Published: December 2017

Statistical analysis of data in published micropuncture studies was applied to determine: a) the number of rats and samples of glomerular capillary pressure (Pg), end-capillary oncotic pressure (COPE), and proximal tubule pressure (Pt), needed in a single study to state with 95% confidence that a measured mean net efferent effective filtration pressure (delta P*E) is within +/- mmHg of any true value, delta PE; b) the effect of intra-animal variation in Pg, COPE, and Pt values on the number of experiments needed; and c) the probability of obtaining a value for delta P*E that meets this criterion in multiple trials. Assuming no intra-animal variation in Pg, Pt, and COPE values and employing published interanimal variances, at least 42 rats should be studied in any series to show that -1 mmHg less than or equal to (delta P*E -- delta PE) less than or equal to 1 mmHg within 95% confidence limits. If intra-animal variances are 60% of the interanimal variances, 67 rats are needed to obtain that degree of confidence when a single measurement of Pt, Pg, and COPE is made in each rat, and 47 animals are required with five measurements per rat. A value for delta P*E within 2-3 mmHg of its true value is, however, attainable with confidence using a far smaller number of animals per series.
Prostaglandin-dependent polyuria in hypercalcemia
Authors: Serros E. R. , Kirschenbaum M. A.
Published: December 2017

The present experiments examined the role of prostaglandin biosynthesis in the increase in urine flow rate seen in rats with hypercalcemia induced by the administration of 1,25-dihydroxycholecalciferol. In a first group, rats receiving the vitamin D metabolite developed hypercalcemia, polyuria, and increased urine prostaglandin E excretion. Indomethacin resulted in a fall in urine prostaglandin E excretion. A second group was fluid restricted to ascertain whether increased thirst could be an etiologic mechanism of the polyuria. This resulted in a trivial fall in urine flow rate despite a fall in body weight and a rise in both urine and plasma osmolality. In a final group, prostaglandin inhibition restored the vasopressin sensitivity of the hypercalcemic kidney. Accordingly, the polyuria seen in hypercalcemic rats after the administration of 1,25-dihydroxycholecalciferol is associated with an increase in urine prostaglandin E excretion and can be reversed by inhibition of prostaglandin synthesis. In addition, this polyuria can occur independent of the thirst mechanism. Finally, there is evidence that the vasopressin resistance of the hypercalcemic kidney could be reversed by prostaglandin inhibition.
Renal hemodynamics and sodium excretion in stroke-prone spontaneously hypertensive rats
Authors: Nagaoka A. , Kakihana M. , Suno M. , Hamajo K.
Published: December 2017

Renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and sodium and water excretion were measured in anesthetized stroke-prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR), and control Wistar-Kyoto rats (WKY) at 9 wk of age. Mean arterial pressure in SHRSP and SHR was significantly higher than that in WKY. RBF was slightly increased in SHR and decreased in SHRSP. RVR was markedly elevated only in SHRSP. In both strains of SHR, GFR was significantly increased but water and sodium excretion were similar. When renal perfusion pressure in both strains of SHR was reduced to a level similar to that of WKY by aortic constriction, RBF was slightly but significantly reduced in both SHRSP and SHR, and GFR only in SHRSP. RVR in SHRSP was still higher. Sodium and water excretion were markedly decreased in both SHR and SHRSP. The data suggest that SHRSP are characterized by an alteration in renal hemodynamics at a young age and support the hypothesis that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.
Dietary chloride modifies renin release in normal humans
Authors: Koletsky R. J. , Dluhy R. G. , Cheron R. G. , Williams G. H.
Published: December 2017

The effect of high and low chloride diets on the responses of plasma renin activity (PRA), angiotensin II (ANG II), and aldosterone (Aldo) to upright posture was studied in the same normal subjects in balance on constant sodium intake. Diet 1 consisted of 10 meq Na/day (low Na) and either 50 or 150 meq Cl/day. Diet 2 consisted of 200 meq Na/day (high Na) and either 20 or 200 meq Cl/day. The mean recumbent PRA level on the high Na-high Cl diet tended to be lower than on the high Na-low Cl diet but was not significantly different. However, the absolute peak upright PRA levels, 8.8 +/- 1.0 vs. 4.4 +/- 0.8 ng . ml-1 . h-1, and the incremental difference (delta PRA) between recumbent and peak upright PRA levels, 5.5 +/- 0.8 vs. 2.2 +/- 0.5 ng . ml-1 . h-1, were significantly less on the high Na-high Cl diet compared with the high Na-low Cl diet. Similar significant changes were seen in ANG II and Aldo levels. However, there were no significant changes in PRA, ANG II, and Aldo responses to upright posture on the low Na diet when the dietary Cl was varied. It is concluded that dietary Cl is another factor modifying renin release. However, Cl is probably less important than Na because Cl-induced changes in PRA were not seen in the low salt state.
Mineralcorticoid receptors along the nephron: [3H]aldosterone binding in rabbit tubules
Authors: Doucet A. , Katz A. I.
Published: December 2017

To identify the site of mineralocorticoid action along the nephron, we measured the specific binding of [3H]aldosterone to nephron segments microdissected from aldosterone-deficient rabbits. Specific binding was defined as the difference between binding measured in the absence or in the presence of 2,000-fold excess of unlabeled hormone (in 10(-18) mol X cm tubule length-1 +/- SE). High specific binding capacity was found in the branched collecting tubule (108 +/- 4), the cortical collecting tubule (119 +/- 9), and the outer medullary collecting tubule (115 +/- 16), whereas specific binding was negligible in the proximal convoluted tubule (8 +/- 9), pars recta (2 +/- 6), medullary thick ascending limb (4 +/- 6), cortical thick ascending limb (6 +/- 2), and distal convoluted tubule (6 +/- 6). In cortical collecting tubules, Scatchard analysis of the specific [3H]aldosterone binding indicated a dissociation constant (KD) of 2.2 X 10(-9) M and a maximum number of binding sites of 157 X 10(-18) mol X cm tubule length-1. The steroid specificity was assessed from the competition of various steroids for [3H]aldosterone binding sites. Receptors from the cortical collecting tubule revealed the following sequence of affinities: aldosterone greater than DOCA greater than spironolactone greater than dexamethasone greater than 5 alpha-dihydrotestosterone = progesterone = 17 beta-estradiol, indicating that the binding sites in the collecting tubule are mineralocorticoid receptors. These results demonstrate significant [3H]aldosterone binding to receptors of high affinity and mineralocorticoid specificity only in the collecting tubule and suggest that this nephron segment is the target site of mineralocorticoid action in the rabbit kidney.
Micropuncture study of the superficial nephron of Perognathus penicillatus
Authors: Braun E. J. , Roy D. R. , Jamison R. L.
Published: December 2017

A micropuncture study of Perognathus penicillatus, a small rodent native to the deserts of the southwestern United States was performed to evaluate the function of the superficial nephron. Data are reported for 12 animals of 17 g average body wt. Mean glomerular filtration rate was 475 +/- 73 microliter X min-1 X g kidney wt-1. Urine osmolality averaged 1,154 +/- 197 mosmol/kg H2O. Single nephron glomerular filtration rate averaged 43 nl X min-1 X g kidney wt-1 in the proximal tubule and 48 in the distal tubule, values that are not significantly different. In terms of the filtered load remaining unreabsorbed at the end of the accessible proximal tubule, the average percentages were 46 water, 48 total solute, 45 sodium, 56 phosphorus, 62 potassium, 71 magnesium, and 54 calcium. The concentrations of potassium and magnesium in fluid samples increased significantly along the proximal tubule. Approximately at the midpoint of the distal tubule, fractional delivery of water, 13.1%, was greater than that for total solute, 10%, or sodium, 7%, indicating that the intervening segment of nephron reabsorbed solute and sodium in excess of water. The function of the superficial nephron resembles that of species previously investigated except for potassium reabsorption in the proximal convoluted tubule.
Differences between renal tubular processing of glucagon and insulin
Authors: Peterson D. R. , Carone F. A. , Oparil S. , Christensen E. I.
Published: December 2017

Renal processing of glucagon and insulin was compared. Iodinated glucagon (mol wt 3,674, linear molecule) or insulin (mol wt 6,000, two chains with disulfide bonds) was microinfused into surface nephrons of the rat kidney, and the radiolabel recovered in the urine was quantified and characterized. Proximal but not distal reabsorption of both peptides was observed, and uptake varied similarly as a function of tubular length. After proximal microinfusion, [125I]glucagon was largely degraded to [125I]tyrosine in the urine, but remained intact after distal infusion. [125I]Insulin was recovered as intact peptide following both proximal and distal microinfusion. Prolonged tubular sequestration of 125I label was observed following proximal microinfusion of [125I]insulin, with efflux requiring longer than 1 h for completion. No measurable cellular sequestration of [125I]glucagon was observed. Incubation of both peptides with rabbit renal microvilli membranes resulted in enzymatic hydrolysis of [125I]glucagon but relatively little or no degradation of [125I]insulin. It is concluded that glucagon and insulin are reabsorbed in the proximal tubule by predominantly different mechanisms.
Interrelationships of ion transport in rat submaxillary duct epithelium
Authors: Knauf H. , Lubcke R. , Kreutz W. , Sachs G.
Published: December 2017

The transport of Na+, K+, Cl-, and HCO3(-) across the epithelium of the rat submaxillary salivary duct is postulated to be due to the coupling of the basolateral Na+-K+-ATPase with various ion transport systems in the luminal and basolateral membranes. Na+ reabsorption depends on the presence of a rheogenic (Na+ conductance) and an electroneutral (Na+:H exchange) pathway, both of which are sensitive to amiloride. K+ secretion is postulated to be mediated by a K+: H+ antiport, coupling between Na+ reabsorption and K+ secretion, thus depending on local H+ ion concentration. The ratio between electroneutral Na+ influx and K+ efflux, therefore, determines the rate of HCO3(-) secretion. In the absence of Na+ influx, although K+ efflux falls, HCO3(-) secretion rises to a value equal to that of K+ secretion. The maintenance of K+ secretion in the absence of luminal Na+ requires an additional Na+-entry step across the basolateral membrane, also postulated to be due to Na+:H+ exchange.
Renal Na-K-ATPase: its role in tubular sodium and potassium transport
Authors: Katz A. I.
Published: December 2017

Na-K-ATPase, the enzymatic equivalent of the sodium:potassium pump, is found in large amounts in the kidney, and this organ has figured prominently both as a source for the purification of the enzyme and as a target for the study of its properties. Located on the basolateral aspect of tubule cells, renal Na-K-ATPase plays a key role in the active translocation of Na and K across this membrane as well as in the "secondary active" transport of a number of other solutes. The activity of renal Na-K-ATPase varies in parallel with sustained changes in Na or K transport, indicating the participation of this enzyme in the chronic adaptation of the kidney to altered Na reabsorption or K secretory load. Because of its slow turnover, however, the role of Na-K-ATPase in the modulation of acute changes in cation transport is unclear. Several hormones and vanadate influence renal Na-K-ATPase activity, and their importance as potential physiologic regulators of this enzyme is examined. Most of the information on the renal enzyme has been obtained from studies using homogenates or subcellular fractions thereof, but more recently the development of tubule microdissection and microanalytic methods has made possible the study of Na-K-ATPase in single nephron segments. This approach has opened new possibilities for evaluating the role of this enzyme in kidney function by facilitating correlation of enzyme activity with transport events in the same structure and by enabling us to focus the study of Na-K-ATPase on discrete anatomic subdivisions of the functionally heterogeneous nephron.
Impact of hydrogen ion on fasting ketogenesis: feedback regulation of acid production
Authors: Hood V. L. , Danforth E. , Horton E. S. , Tannen R. L.
Published: December 2017

To determine whether acid-base balance regulates hydrogen ion production, seven obese volunteers were given NaHCO3 and NH4Cl (2 mmol.kg-1.day-1) during two separate 7-day fasts. On days 5-7 plasma bicarbonate was lower in the NH4Cl fasts (14.0 +/- 1.4 mM) than in the NaHCO3 fasts (18.3 +/- 1.1 mM), while urine pH and net acid excretion did not differ. Acid production (acid excretion minus intake) was greater by 204 mmol/day in the NaHCO3 fasts (274 +/- 16 mmol/day) than in the NH4Cl fasts (70 +/- 19 mmol/day). Ketoacid excretion, which reflected net ketoacid production, paralleled acid production, decreasing from 213 +/- 24 mmol/day in the NaHCO3 fasts to 67 +/- 18 mmol/day in the NH4Cl fasts. Thus, during starvation, alterations in hydrogen ion intake and the associated changes in acid-base balance modify the net production of endogenous acid by influencing the synthesis or utilization of ketoacids. Although the specific site of this metabolic regulation is undefined, these results indicate that systemic acid-base status can exert feedback control over hydrogen ion production.
Calcium-prostaglandin interaction on the action of antidiuretic hormone in the dog
Authors: Berl T. , Erickson A. E.
Published: December 2017

The effect of interaction between calcium and prostaglandin (PG) on the action of antidiuretic hormone (ADH) was studied in the water-diuresing anesthetized dog. Maximal urinary osmolality after 100 mU or ADH was 331 +/- 24 in the normocalcemic state versus only 228 +/- 31 mosmol/kg (P less than 0.01) in dogs made acutely hypercalcemic when their serum Ca concentration was increased from 8.9 +/- 0.2 to 11.6 +/- 0.4 mg/100 ml (P less than 0.001). To define the role of PG in this effect, studies were performed in the presence of PG inhibition with indomethacin (10 mg/kg). The antidiuretic response to 100 mU of ADH was decreased by hypercalcemia, as maximal osmolality was 1,096 +/- 65 in the normocalcemic PG-inhibited dog but only 555 +/- 50 mosmol/kg in the acutely hypercalcemic PG-inhibited dog (P less than 0.001). Conversely, the effect of PG inhibition to enhance the hydroosmotic effect of ADH was also demonstrable in acutely hypercalcemic dogs, as maximal urinary osmolality following 100 mU of ADH was 257 +/- 9 before and 557 +/- 60 mosmol/kg after PG inhibition (P less than 0.001). These studies demonstrate, therefore, that the effect of acute hypercalcemia on the hydroosmotic response to vasopressin is not dependent on the synthesis of an endoperoxide metabolite. Likewise, hypercalcemia blunts but does not abolish the effect of PG inhibitors to potentiate the hydroosmotic effect of ADH.
Cell osmotic water permeability of isolated rabbit proximal straight tubules
Authors: Gonzalez E. , Carpi-Medina P. , Whittembury G.
Published: December 2017

Proximal straight tubules were dissected and mounted in a chamber with their lumina occluded. The well-stirred bath could be 95% changed within 84 ms to set up osmotic gradients (delta Coi) across the peritubular cell aspect. Volume changes (less than or equal to 10 pl/mm) were estimated from continuous records of diameter changes (error less than 0.1 micrometers). delta Coi greater than or equal to 2-3 mosM could be discerned. delta Coi values from 10 to 44 mosM were used to evaluate Posc, the cell osmotic water permeability coefficient, and extrapolated to delta Coi = 0. Posc = 25.1 (+/- 2.3) X 10(-4) cm3.s-1.osM-1.cm2 tubular surface area-1. These values are lower than those reported for Pose, the transepithelial osmotic water permeability coefficient, and become lower if corrected for the real (infolded) peritubular cell surface area. Thus, for a given osmotic difference, transcellular water flow finds a higher resistance than paracellular water flow. Experiments were also performed with delta Coi greater than 100 mosM, but interpretation of these data is difficult because of the presence of volume regulatory phenomena and other undesirable effects.
In vivo biosynthesis and turnover of glomerular basement membrane in diabetic rats
Authors: Cohen M. P. , Surma M. L. , Wu V. Y.
Published: December 2017

Glomerular basement membrane (GBM) was labeled in vivo by the injection of tracer amounts of tritiated proline into normal and streptozotocin-diabetic rats. Basement membrane biosynthesis and turnover were determined from the specific activities of proline and hydroxyproline in samples purified following osmotic lysis of glomeruli isolated 4 h to 12 days after injection. Peak radiolabeling of normal and diabetic GBM occurred within 24-48 h and 48-72 h, respectively, and, when corrected for differences in the serum proline specific activities, [3H]proline incorporation was greater in diabetic than in normal samples. In contrast to the subsequent time-dependent progressive decline in radiolabeling in basement membranes from normal animals, specific activities of proline and hydroxyproline in diabetic glomerular basement membrane did not change significantly over the same period of observation. Renal cortical mass and glomerular basement membrane collagen content were preserved in diabetic animals despite loss of body weight. The findings are compatible with prolongation of glomerular basement membrane turnover in experimental diabetes, and suggest that diminished degradation contributes to the accumulation of glomerular basement membrane that is characteristic of chronic diabetes.
Heterogeneity of sodium-dependent D-glucose transport sites along the proximal tubule: evidence from vesicle studies
Authors: Turner R. J. , Moran A.
Published: December 2017

The glucose transport properties of brush border membrane vesicles from the outer cortex (early proximal tubule) and outer medulla (late proximal tubule) of rabbit kidney were studied. In the outer cortical preparation the behavior of the sodium-dependent component of D-glucose flux indicated the presence of a low-affinity transport system with Km congruent to 6 mM and Vmax congruent to 10 nmol.min-1.mg protein-1 as measured under zero trans conditions at 40 mM NaCl and 17 degrees C. By contrast, in the outer medullary preparation this component of flux behaved as a high-affinity system with Km congruent to 0.35 mM and Vmax congruent to 4 nmol.min-1.mg protein-1. Differences in transport specificity between the two preparations were also indicated and glucose uptake by the outer cortical vesicles was significantly more sensitive to inhibition by phlorizin. These results suggest the existence of two distinct sodium-dependent D-glucose transport systems in the renal proximal tubule brush border membrane. The kinetic studies presented here were done under zero trans sodium and glucose conditions. The rationale and methodology for carrying out these measurements reliably are discussed in detail.
Na+ transport properties of the peritubular membrane of cortical collecting tubule
Authors: Natke E. , Stoner L. C.
Published: December 2017

The effects of varying endogenous aldosterone levels on the passive and active properties of the peritubular membrane were studied. Rabbits that were fed either a low Na+ (normal K+) diet or a high Na+, low K+ diet increased or decreased plasma aldosterone, respectively. Tubules were dissected, filled with oil, and incubated in 0 K+ medium to increase intracellular sodium. Cellular sodium and potassium content was measured by helium-glow photometry. The degree to which cells accumulate sodium and lose potassium is a function not only of time of exposure but also of diet. Tubules from animals on a low Na+ diet are about 6 times more permeable to sodium than those from animals fed a high Na+ diet. When tubules were loaded with sodium and returned to a normal (5 mM K+) bathing medium, net sodium efflux and potassium influx occurred. The rate of sodium efflux by cortical collecting tubules dissected from animals on the low Na+ diet was 2.3 times greater than the efflux rate of tubules from animals on the high Na+ diet. These data suggest that high levels of endogenous aldosterone enhance sodium transport measured in vitro across the peritubular membrane of cortical collecting tubule.
Oscillations of plasma K+ and insulin during K+ infusion in awake anephric dogs
Authors: Sterns R. H.
Published: December 2017

Changes in plasma potassium ([K+]p) and insulin levels were monitored during K+ infusion in awake and anesthetized nephrectomized, splenectomized dogs. In dogs studied while anesthetized with pentobarbital, the increase in [K+]p was linear, reflecting a nearly constant rate of cellular uptake of the infused K+. In contrast, in dogs studied 18 h after nephrectomy while awake, [K+]p oscillated during infusion, reflecting an inconstant rate of cellular K+ uptake. Although these oscillations in [K+]p were associated with parallel oscillations in plasma insulin levels (suggesting the possibility of a physiological feedback control loop involving K+ and insulin), when the oscillations in insulin levels were blunted by somatostatin infusion or abolished by pancreatectomy plus insulin replacement, oscillations in [K+]p persisted and the average rate of cellular K+ uptake was not diminished. The observed oscillations of [K+]p during K+ infusion suggest the possibility of regulatory control of cellular K+ uptake within the pathophysiologic range of [K+]p. The putative control system is independent of and quantitatively more important than K+-induced insulin secretion and is obscured by pentobarbital anesthesia.
Mechanism of potassium adaptation
Authors: Hayslett J. P. , Binder H. J.
Published: December 2017

After chronic dietary potassium loading, epithelia in distal portions of the nephron and large intestine adapt to increase the rate of potassium secretion. This response to increased excretory loads of potassium maintains overall external balance and protects against the potentially lethal effects of hyperkalemia. The cellular adaptation in epithelia involved in preserving potassium homeostasis during potassium loading is characterized by an increase in the number of potassium pumps, reflected by an increase in Na-K-ATPase activity, in the basolateral cell membrane due, at least in part, to an amplification in the area of this membrane, and by an increase in transepithelial potential difference in most, but not all, adapted epithelia. These changes suggest that potassium adaptation is due to a step-up in the rate of cell uptake of potassium. In addition to chronic dietary loading, other conditions such as chronic renal insufficiency, elevated levels of mineralocorticoids, and administration of glucocorticoids are also characterized by accelerated rates of potassium secretion in the distal nephron and colonic mucosa and stimulation of Na-K-ATPase in basolateral portions of the cell membrane. These cellular changes in epithelia with increased capacity for potassium secretion are discussed in the context of our present understanding of mechanisms that control potassium excretion in urine and feces.
Metabolic inhibitors: effects on metabolism and transport in the proximal tubule
Authors: Gullans S. R. , Brazy P. C. , Soltoff S. P. , Dennis V. W. , Mandel L. J.
Published: December 2017

This study examined the effects of the metabolic inhibitors rotenone and antimycin A on oxidative metabolism and transport in the proximal renal tubule of the rabbit. Measurements of oxygen consumption rate (QO2), cellular ATP content, and mitochondrial NAD redox state were made in suspensions of renal cortical tubules. Parallel experiments were conducted in isolated perfused proximal convoluted tubules to measure the absorption rates of fluid (Jv), phosphate (JlbPO4), and glucose (JlbGlc). The results indicate that rotenone and antimycin A, at doses (10(-6) M) that maximally inhibited mitochondrial oxidative phosphorylation, abolished net fluid and phosphate absorption and nearly eliminated net glucose transport. Partial inhibition of oxidative metabolism with 10(-7) M rotenone caused proportional reductions in QO2, ATP content, and Jv; however, JlbPO4 was reduced more markedly than either Jv or JlbGlc. We conclude that rotenone and antimycin A inhibit the sodium-dependent transport of fluid, phosphate, and glucose by blocking mitochondrial ATP production. Furthermore, the inhibition of mitochondrial oxidative metabolism and the inhibition of net sodium transport are closely correlated.
Effect of obstruction on ureteral circumferential force-length relations
Authors: Biancani P. , Hausman M. , Weiss R. M.
Published: December 2017

After 2 wk of obstruction, rabbit ureteral length increases by 24%, outer diameter by 100%, and cross-sectional muscle area by 248%. In addition to undergoing muscle hypertrophy, obstructed ureters developed greater circumferential contractile forces than control ureters. The peak active force of obstructed ureteral segments was approximately twice that of control ureters. The increase in force was associated with a corresponding doubling of active circumferential stress (force/unit area), suggesting that the force increase resulted from 1) an increase in contractility rather than being a reflection of the muscle hypertrophy that occurred with obstruction, and 2) muscle fiber reorientation. Thus, the ureter, dilated secondary to 2 wk of obstruction, is not mechanically decompensated bur rather undergoes changes that result in an increase in contractility, Despite muscle hypertrophy and increased contractility, the obstructed ureter's ability to develop the intraluminal pressures required for urine transport decreases. The decrease in intraluminal pressure despite an increase in contractility results from the increased ureteral diameter following obstruction according to the Laplace relationship.
Improved function with amino acids in the isolated perfused kidney
Authors: Epstein F. H. , Brosnan J. T. , Tange J. D. , Ross B. D.
Published: December 2017

When isolated rat kidneys are perfused with glucose as the only substrate, there is a progressive diminution in glomerular filtration rate and fractional reabsorption of sodium. This is most marked after 1 h. Renal glutathione content rapidly falls and is less than 30% of control levels after 1 h. Renal concentrating ability is markedly impaired and structural lesions are consistently observed in cells lining the thick ascending limb of Henle's loop. Addition of 20 physiologic amino acids including cysteine to the perfusate prevents the fall in renal glutathione, prevents the anatomical damage to ascending limb cells, permits GFR and fractional sodium reabsorption to remain high and close to their initial levels for as long as 4 h, and improves renal concentrating capacity. If amino acid supplementation is limited to three precursors of glutathione--cysteine, glycine, and glutamic acid--renal glutathione content is preserved and concentrating ability is improved, but GFR and fractional sodium reabsorption are not maintained as well as with comprehensive amino acid supplements. The results suggest that amino acid deficiency and glutathione depletion may contribute to disturbances in renal structure and function.
Acetylcholine-induced vasodilation without natriuresis during control of interstitial pressure
Authors: Hartupee D. A. , Burnett J. C. , Mertz J. I. , Knox F. G.
Published: December 2017

Increased renal blood flow and increased renal interstitial pressure have been proposed as mechanisms for the natriuresis caused by vasodilation with acetylcholine. We tested the hypothesis that the natriuresis due to acetylcholine is associated with the increase in interstitial pressure rather than with the increase in blood flow. Experiments were performed in decapsulated kidneys that, along with partial aortic clamping, allowed dissociation of the increases in renal interstitial pressure and blood flow. At the beginning of intrarenal acetylcholine infusion (2 micrograms . kg-1 . min-1), the aorta was clamped so that a vasodilation occurred without an increase in interstitial pressure. A response to acetylcholine was also obtained when interstitial pressure was allowed to increase. During this response, renal blood flow, interstitial pressure, and fractional sodium excretion increased. During control of interstitial pressure, renal blood flow increased, but fractional sodium excretion did not change. Thus, when interstitial pressure was controlled, the acetylcholine-induced vasodilation did not result in an increase in fractional sodium excretion. These results demonstrate that an increase in renal interstitial pressure is required for the natriuresis associated with acetylcholine-induced vasodilation.
Evaluation of bicarbonate transport in rat distal tubule: effects of acid-base status
Authors: Lucci M. S. , Pucacco L. R. , Carter N. W. , DuBose T. D.
Published: December 2017

Previous micropuncture studies utilizing indirect methods to estimate bicarbonate transport in the rat superficial distal tubule have indicated that the distal bicarbonate reabsorptive process normally operates well below the saturation level. Recent studies from our laboratory failed to demonstrate a spontaneous acid disequilibrium pH in this segment, implying that the bicarbonate reabsorptive rate was less than previously estimated. The purpose of the present experiments were 1) to measure the rate of absolute bicarbonate reabsorption by the rat superficial distal tubule while controlling bicarbonate delivery, and 2) to examine the effects of alterations in acid-base status on the rate of bicarbonate reabsorption. Five groups of rats in different states of acid-base balance were studied. No significant bicarbonate reabsorption was detected in the control hydropenic, combined respiratory acidosis-metabolic alkalosis, acute respiratory acidosis, or acute metabolic acidosis groups. In contrast, metabolic acidosis of 3 days duration resulted in a significant bicarbonate reabsorptive rate of 52.6 +/- 13.9 pmol . mm-1 . min-1. The observation of significant bicarbonate reabsorption in the distal tubule only during chronic metabolic acidosis of 3 days duration is compatible with adaptation of this normally low-capacity segment to chronic changes in systemic acid-base states.
Independence of beta-adrenergic stimulation of renin release on renin synthesis
Authors: Katz S. A. , Malvin R. L.
Published: December 2017

Rat renal cortical slices incubated in vitro released 7.0 +/- 0.5% (mean +/- SE, n=30) of their total renin content into the incubation medium in 1 h. Isoproterenol (10-6 M), a beta-adrenergic agonist, caused a 75 +/- 17% (n=7) increase in renin release from the cortical slices. Treatment of the cortical slices with either cycloheximide or puromycin caused a significant 96.2 +/- 0.34 (n=8) or 98.5 +/- 0.3% (n=5), respectively, inhibition of protein synthesis. After protein synthesis and presumably renin synthesis was blocked with either cycloheximide or puromycin, isoproterenol was still able to increase significantly renin release from the cortical slices despite almost total blockade of protein synthesis. We conclude that a storage pool of renin content is released may exist, since 1) only 7.0 +/- 0.5% of the cortical slice renin content is released each hour, and 2) isoproterenol stimulation of renin release is not acutely dependent on renin synthesis. It is hypothesized that beta-adrenergic stimulation of renin release is elicited from a storage pool of previously synthesized renin.
Glucocorticoid stimulation of Na-K-ATPase in superfused distal segments of kidney tubules in vitro
Authors: Rayson B. M. , Edelman I. S.
Published: December 2017

The ability of glucocorticoids to regulate Na-K-ATPase activity directly was assessed in separated rat kidney tubules derived from the distal nephron. These tubules were superfused under sterile conditions and maintained in a viable condition for at least 24 h in a newly devised apparatus. Viability was assessed by measuring O2 consumption, protein/DNA ratios, and Na-K-ATPase and Mg-ATPase activities. At a concentration of 10(-8) M, dexamethasone elicited a 27% increase in tubular Na-K-ATPase activity in 6 h and a 32% increase in 24 h. In a separate series, assayed at 24 h, the maximal effect was obtained at a dexamethasone concentration of less than 10(-8) M, and by inspection half-maximal stimulation was obtained at approximately 10(-9) M. At a concentration of 10(-7) M, 17 beta-estradiol, testosterone, progesterone, and deoxycorticosterone acetate had no significant effect on tubular Na-K-ATPase activity. These results as well as the time-course and dose-response data imply that the response is mediated by the glucocorticoid receptor pathway. Since the magnitude of response in vitro was similar to the one obtained after injection of dexamethasone in vivo, much if not all of the action appears to be direct and independent of glucocorticoid-induced changes in the filtered Na+ load.
Slow rise and diurnal change of blood pressure with saralasin and angiotensin II in rats
Authors: Brown A. J. , Clark S. A. , Lever A. F.
Published: December 2017

Our objectives were to determine whether saralasin, like angiotensin II, raises blood pressure gradually when given by constant infusion and whether either agent alters the diurnal variation of arterial pressure. Eight female Wistar rats were infused intravenously with 5% dextrose for 2 days, then with saralasin at 10 micrograms . kg-1 . min-1 for 4 days, and finally with dextrose for 2 days. Six other rats were infused with angiotensin II (20 ng . kg-1 . min-1) instead of saralasin. Mean arterial pressure (MAP) was recorded continuously. Saralasin and angiotensin II gradually raised MAP in all rats, by 22.0 mmHg on the 4th day of saralasin and by 41.7 mmHg on the 4th day of angiotensin II. Both agents also increased the diurnal variation of blood pressure, MAP increasing 8.3-20.6 mmHg during the night and falling 6.7-19.1 mmHg during the day. Variability of arterial pressure was also increased by saralasin and in an earlier experiment by angiotensin II. We conclude that saralasin has a slow pressor action similar to that of angiotensin II but distinct in its timing both from the rapid agonist action of saralasin and from the acute vasoconstrictor action of angiotensin II. These effects of saralasin may compromise interpretation of experiments in which the drug is given by prolonged infusion to assess the role of angiotensin II.
Adaptation of deep and superficial nephrons to changes in dietary phosphate intake
Authors: Haramati A. , Haas J. A. , Knox F. G.
Published: December 2017

Dietary phosphate intake is now recognized to be a primary regulator of renal phosphate excretion. However, the nephron sites involved in the adaptation to changes in dietary phosphate are unclear. We tested the hypothesis that deep and superficial nephrons respond differently to changes in dietary phosphate by comparing fractional phosphate delivery (FDP%) from proximal tubules of both nephron populations. Because phosphate reabsorption is not detectable in the ascending loop of Henle, FDP% to the superficial early distal tubule and papillary loop of Henle reflect delivery from superficial and deep nephron proximal tubules, respectively. Micropuncture experiments were performed in 17 acutely TPTX rats fed either a low (0.07%) or a high (1.8%) phosphate diet for 4 days prior to the experiment. In low phosphate diet, fractional phosphate excretion was 0.93 +/- 0.26%. FDP% was 7.5 +/- 0.5 and 9.1 +/- 2.2% from superficial and deep nephron proximal tubules, respectively (P greater than 0.05). In high phosphate diet, fractional phosphate excretion was 29.6 +/- 5.0%. FDP% was significantly greater from superficial proximal tubules, 33.9 +/- 4.6%, compared with that from deep nephron proximal tubules, 14.0 +/- 2.7% (P less than 0.05). We conclude that significant adaptation of phosphate reabsorption in response to changes in dietary phosphate intake occurs in the superficial but not in the deep nephron proximal tubule in acutely TPTX volume-expanded rats. In addition, the presence of distal phosphate reabsorption was not evident in high phosphate diet but must occur in low phosphate diet.
Renal contribution to acid-base regulation during the menstrual cycle
Authors: Takano N. , Kaneda T.
Published: December 2017

Menstruating women exhibit a light but sustained hypocapnia during the luteal phase. To elucidate whether the hypocapnia results primarily from a respiratory or renal mechanism, we measured the rate of urinary excretion of acid at intervals during the menstrual cycle in five subjects. The acid-base composition of arterial blood in three subjects and end-tidal PCO2 in the remaining two subjects were also determined. During the follicular phase, the acid-base composition of blood and the rate of net acid excretion remained virtually constant. After ovulation, significant decreases in PaCO2 (3.5 mmHg), [HCO3]p (2 meq/liter), and net acid excretion (2 meq/h) occurred in the first 4-6 days of the luteal phase (14 days long). Following this, net acid excretion returned to the preovulatory level. PaCO2 and [HCO3]p, however, remained decreased for 3 more days. At the end of the luteal phase, restoration of PaCO2 proceeded faster than that of [HCO3]p. The acid-base changes in blood and urine observed during the luteal phase were comparable to those occurring during adaptation and recovery from sustained hypocapnia, suggesting that hypocapnia during the luteal phase is primarily respiratory in origin.
Interaction of renal beta 1-adrenoceptors and prostaglandins in reflex renin release
Authors: Kopp U. , DiBona G. F.
Published: December 2017

Anesthetized dogs with isolated carotid sinus preparation were used to examine the mechanisms involved in the increase in renin secretion rate produced by carotid baroreceptor reflex renal nerve stimulation (RNS) at constant renal perfusion pressure. Lowering carotid sinus pressure by 41 +/- 5 mmHg for 10 min increased mean arterial pressure and heart rate, caused no or minimal renal hemodynamic changes, decreased urinary sodium excretion, and increased renin secretion rate. Metoprolol, a beta 1-adrenoceptor antagonist, given in the renal artery, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,764 +/- 525 to 412 +/- 126 ng/min (70 +/- 8%). Indomethacin or meclofenamate, prostaglandin synthesis inhibitors, did not affect the decrease in urinary sodium excretion but attenuated the increase in renin secretion rate, from 1,523 +/- 416 to 866 +/- 413 ng/min (51 +/- 18%). Addition of metoprolol to indomethacin-pretreated dogs attenuated the increase in renin secretion rate from 833 +/- 327 to 94 +/- 60 ng/min (86 +/- 10%). These results indicate that reflex RNS at constant renal perfusion pressure results in an increase in renin secretion rate that is largely mediated by renal beta 1-adrenoceptors and is partly dependent on intact renal prostaglandin synthesis. The beta 1-adrenoceptor-mediated increase in renin secretion rate is independent of and not in series with renal prostaglandins.
Effect of calcitonin on urine concentration in the rat
Authors: Carney S. , Morgan T. , Ray C. , Thompson L.
Published: December 2017

Because mammalian distal nephron segments with both calcitonin- and antidiuretic hormone- (ADH) sensitive adenylate cyclase activity have been described, in vivo and in vitro experiments were performed to study the effect of calcitonin on rat distal nephron water permeability. Calcitonin 1 and 0.1 U/ml, but not 0.01 U/ml, significantly increased the diffusional water permeability in the isolated papillary collecting duct by 15 and 11%, respectively. However, this effect was small when compared with a 68% increase with a supramaximal concentration of ADH (from 4.0 +/- 0.3 to 6.7 +/- 0.9 microns/s; n = 6, P less than 0.01). The normal increase in water permeability with increasing concentration of ADH (0.02 and 0.2 mU/ml) was depressed by the previous addition of calcitonin (1 U/ml) to the bath but was unaltered with the supramaximal ADH concentration (2 mU/ml). Verapamil, a compound that antagonizes cellular calcium entry, did not alter the effect of calcitonin on diffusional water permeability. Calcitonin in concentrations of 0.05, 0.5, and 5 U/ml produced a significant reduction in urine flow and free water clearance. Pretreatment with calcitonin in these concentrations inhibited the antidiuretic action of ADH. These studies suggest that calcitonin acts as a partial agonist to ADH within the distal nephron. It is unclear whether such an action represents a physiological or a pharmacological effect.