The renal metabolism and handling of [1,2-3H]aldosterone ([3H]A) was studied using isolated perfused rat kidney under different perfusion conditions. The metabolite production rate (MPR) and the urinary excretion of [3H]A together with its radiometabolites (UV/P3H) were studied. Among the formed metabolites, no acid-labile conjugate of aldosterone (ALC) was detected. The MPR was not altered in studies using nonfiltering kidney, a result that suggests that the majority of metabolites were formed without requirement of the process of glomerular filtration and tubular uptake of the hormone. High perfusion pressure (high PP) resulted in a striking increase in whole metabolic clearance rate of aldosterone (MCR[3H]A) due mostly to an enhanced urinary excretion of intact aldosterone and, to a lesser degree, to a significant increase in MPR. Factors determining the excretion rate of [3H]A and its metabolites were than investigated under administration of diuretics. Mannitol (44 mM) induced a marked increase in urine volume (UV) accompanied by a significant UV/P3H increase. Meanwhile, 0.1 mM furosemide resulted in an increase only in UV, but not in UV/P3H. These results revealed the UV dependence of aldosterone excretion in certain diuretic conditions.

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1. Renin release from the isolated perfused rat kidney was markedly stimulated by isoprenaline or anoxia. Renin secreted into the blood-free perfusate was not activated by exposure to cold or dialysis to pH 3.3, suggesting the absence either of cryo-or acid-activatable renin or of factors necessary to activate inactive renin.2. Trypsin treatment did not change renin concentration in the perfusate samples.3. When binephrectomized rat plasma was added to perfusate samples before dialysis, renin concentration in the acidified samples was significantly higher than in samples dialysed to pH 6.5. Diminished renin recovery in the latter samples caused this difference. Binephrectomized rat plasma itself had no significant renin activity before or after acid dialysis, indicating the absence of any important extrarenal source of active or acid-activatable renin in rats.4. Acidification of binephrectomized rat plasma before its addition to the perfusate samples markedly reduced the difference between renin recovery during dialysis to pH 3.3 and dialysis to pH 6.5, indicating that acidification irreversibly inhibited renin inactivation by binephrectomized rat plasma. No net increase in renin concentration was observed in any of our experiments.5. These results suggest that rat kidney does not secrete inactive renin. They also point to the existence of renin inactivation by rat plasma at Correspondence: Dr Haruyuki Nakane, INSERM U36, 17, rue du Fer-a-Moulin, 75005 Paris, France. neutral pH, which might lead to overestimation of acid-activatable renin in rats.

Renin secretion was compared in vivo and in vitro among five groups of rats, each group subjected to a different sodium balance for 10 to 14 days. The state of the renin-angiotensin system in vivo was evaluated by measuring the renal renin (RR) and the plasma renin concentration (PRC) in both anesthetized and nonanesthetized animals. The in vitro renin secretion rate (RSR) was determined in isolated perfused kidneys. RR was reduced (-48%) by sodium loading and deoxycorticosterone (DOCA) and increased (+27%) by sodium deprivation and furosemide. Sodium loading and DOCA reduced both the PRC and the RSR to less than 20% of control values. By contrast, sodium deprivation and furosemide induced a more than fourfold rise in the PRC but only a small increase in the RSR (+37%). These results indicate that changes in fractional renin release are induced by sodium balance variation, and these changes are preserved in vitro only in sodium-loaded states. The inability of sodium-deprived kidneys to maintain high renin release in vitro suggests that high plasma renin levels in these rats depend on mechanisms that are not preserved in vitro. There was no evidence supporting the participation of inactive renin secretion in the regulation of fractional renin release under varying sodium balance.