The effect of Ca concentrations in the incubation medium and of estimated intracellular Ca concentrations on renin release was examined with use of pig renal cortical slices. In addition, the Ca requirement for the epinephrine stimulatory effect and for the ouabain inhibitory action on renin release was also tested. In mediums containing 5.9 mM K, variations in Ca concentration had no effect on renin release. In contrast, when the K concentration was 59 mM, a significant inhibition of renin release was attained with all concentrations of calcium. The inhibition of renin release in high K mediums by Ca was attributed to an increase in the intracellular Ca concentration. In addition, both the stimulatory effect of epinephrine and the inhibitory effect of ouabain on renin release required Ca in the medium. These results support the hypothesis that the control of renin secretion is mediated, in part, by changes in the intracellular concentration of Ca, most likely in the juxtaglomerular cells.

Various parameters of renal function were studied before, during, and after the infusion of physiological increments of angiotensin II directly into one renal artery of anesthetized dogs. During water diuresis and during antidiuresis induced with exogenous antidiuretic hormone (ADH), angiotensin II consistently reduced UNaV, UKV, and CPAH, and increased the filtration fraction in the infused kidney. Urinary osmolality was increased only in the presence of ADH, while during water diuresis angiotensin II had no apparent effect on urinary osmolality or flow rate. During saline diuresis, a mean increment of angiotensin II concentration of 14 pg/ml was sufficient to significantly reduce UNaV and urinary flow rate. Changes in CCr, CPAH, and filtration fraction did not correlate with changes in sodium excretion, and intracortical distribution of blood flow remained unaltered. These data support the hypothesis that normal circulating levels of angiogensin II play a direct renal role in the control of sodium, potassium, and water homeostasis, and that angiotensin II exerts a direct, stimulatory effect on tubular sodium reabsorption independent of changes in GFR, RPF, filtration fraction, or intracortical distribution of blood flow.

Localization of transtubular transport of substances along the nephrons of a pentobarbitalized dog is characterized by allowing concentration patterns to develop during stopped tubular flow (ureteral occlusion with stopped filtration). Previous administration of an osmotic diuretic mannitol provides a watery menstruum against which characteristic concentration patterns are developed point to point along the nephrons. On release of occlusion the diuretic flush washes the concentration pattern along each nephron. Serial urine samples, delivered from a polyethylene catheter, segment this pattern into an ordered array. Plots against time show distortion of the concentration pattern due to variable flow rate. The filtration indicator inulin is injected late after occlusion to reach the filter surfaces and to signal new entry of filtrate into the urine samples after the occlusion is released. The rising concentration pattern of this inulin delineates the randomizing effect of variable lengths among nephrons. Para-aminohippurate (PAH) injected after occlusion signals entry sites for secretion. These appear ahead of inulin. If glucosuria is developed before occlusion such that the glucose reabsorptive transfer maximum is exceeded, the occlusion now allows further time for lowering of glucose concentration along the tubule. The lowered glucose concentration pattern overlaps that of rising PAH, the PAH here being continuously infused beginning before occlusion. PAH secretion is proximal in the mammal. Very distal fluid is relatively sodium free; Na concentrations in proximal areas are not lowered below that accomplished during free diuretic flow. Phosphate shows only reabsorption and a proximal area overlapping glucose. Total measured blood flow is unimpaired during 8-minute occlusions. Plasma PAH extraction ratios are unchanged. Postocclusively injected K42 and Na24 reach all stop flow samples. Evidently peritubular blood flow continues to reach all points along the nephron.

Creatinine and inulin clearances were compared in anesthetized male and female rats. Continuous intravenous infusion, midpoint arterial blood sampling, and ureteral catheterization aided accurate measurements. Average inulin clearances were 1.0 ml/min per 100 g. In the control male rat the creatinine clearance persistently exceeded that of inulin. The elevated CCr: CIn ratio could be reduced to 1 by probenecid, PAH, mercury, or high plasma levels of creatinine. In females a single intramuscular dose of testosterone elevated the ratio to that seen in male rats. This effect declined within 6 hr. Manipulations with steroids other than testosterone did not affect results in either sex. It is suggested that male rats secrete creatinine under the influence of androgens and that inulin is therefore a better measurement of the glomerular filtration rate in the male rat.

We measured the effect of a constant infusion of rat atrial extract on the glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma renin concentration (PRC) of bioassay rats. The infusion rate of the atrial extract was 0.038 ml/min, which represented 1.25 mg of homogenized atrial tissue/min. To ensure that dead space was cleared, clearance measurements during the atrial extract infusion were not begun until urine flow had increased and 300 microliter of urine had been excreted. In the first series of rats, control GFR was 0.69 +/- 0.05, increased to 1.04 +/- 0.06 during infusion of atrial extract, and then decreased to 0.72 +/- 0.08 ml X min-1 X 100 g-1 during the recovery period. In a second series, RPF was also measured. GFR increased from 0.92 +/- 0.02 to 1.15 +/- 0.05 ml X min-1 X 100 g-1, while RPF was unchanged. In both series, the increase in GFR was statistically significant. Constant infusion of atrial extracts had no significant effect on PRC. These studies provide evidence that an atrial factor can cause a large increase in GFR, which may contribute to the natriuretic effect of atrial extracts.