Potassium-sparing effect of trilostane in hydrochlorothiazide-treated rats and dogs.
Trilostane, which inhibits three beta-hydroxysteroid dehydrogenase and aldosterone synthesis in rats and monkeys, significantly attenuated the oral potassium-wasting effect of hydrochlorothiazide (HCTZ) in rats and dogs when coadministered with the diuretic. The steroid reduced the kaliuretic and enhanced the natriuretic (and hyperreninemic) activity of HCTZ in rats, thereby promoting the urinary sodium/potassium ratio. Trilostane completely prevented HCTZ-induced hypokalemia in dogs and tended to reduce the degree of secondary aldosteronism. The combination also promoted hematocrit of dogs by 8% and decreased serum Na+ concentration by 7 meq/liter. When administered alone, trilostane increased canine serum potassium levels slightly and promoted rat urinary Na+/K+ ratio. Results confirm previous reports of antikaliuretic activity of trilostane in diuretic-treated rats. Further, the data indicate that frank hypokalemia induced in dogs by hydrochlorothiazide can be prevented by adjunctive trilostane therapy without eliciting hyperkalemia.
D000450:Aldosterone / Q000097:blood; D000818:Animals; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D006400:Hematocrit; D006852:Hydrochlorothiazide / Q000037:antagonists & inhibitors*; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine*; D051381:Rats; D012083:Renin / Q000097:blood
D013196:Dihydrotestosterone; D006852:Hydrochlorothiazide; D000450:Aldosterone; D012083:Renin; C009954:trilostane; D011188:Potassium; D006854:Hydrocortisone