Aldosterone antagonism studies in the rhesus monkey.

Renal studies in femal rhesus monkeys indicated that 10 micron g was an optimum i.m. sodium-retaining dose of aldosterone. Aldosterone was injected i.m. at dosages of 2.5, 5, 10 and 20 micron g/animal. The 10-micron g dose induced about a 50% reduction in sodium excretion (from 3.7 to 1.7 mEq/6 hr) and was selected as the standard dose for antagonism studies. K excretion and urine volume remained unchanged. Subsequently, the oral antialdosterone activities of spironolactone and canrenone, a delta6 metabolite, were assessed at dosages of 1, 4 and 8 mg/kg. Dose-related increases in the aldosterone-depressed urinary Na/k ratio occurred primarily as a consequence of enhanced sodium excretion. Canrenone possessed antialdosterone potency equal to that of spironolactone. In the absence of exogenous aldosterone, spironolactone (16 mg/kg) was essentially devoid of diuretic activity whereas hydrochlorothiazide (1 mg/kg) induced marked increases in Na (256%) and K (105%) excretion and urine volume (109%).