Effect of spironolactone on electrolytes, renin, ACTH and corticosteroids in the rat.
Spironolactone (S), known to act as a mineralocorticoid antagonist, has been shown in some circumstances to inhibit steroid biosynthesis. To investigate these two actions in vivo in the rat, animals fed a normal or low Na+ diet were treated with S for 7 days. In animals fed a normal Na+ diet, urinary and faecal electrolytes, aldosterone and corticosterone excretion were measured daily, plasma renin, aldosterone, corticosterone, ACTH, progesterone, DOC and 18-OH-DOC were determined after 4 and 7 days of treatment. In animals fed a low Na+ diet, urinary electrolytes were measured daily and plasma and urinary aldosterone and corticosterone were determined at intervals during the introduction of the diet and in the course of treatment. On a normal Na+ diet, S induced a slight non significant rise in the urinary Na+/K+ ratio on the first day of treatment, no change in faecal electrolyte excretion, and a sustained increase in aldosterone but not in corticosterone excretion. It produced a 6-fold elevation in plasma aldosterone levels, a less marked rise in renin and progesterone, a delayed increase in DOC and no change in ACTH, 18-OH-DOC or corticosterone concentration. On a low Na+ diet, treatment induced a rise in the urinary Na+/K+ ratio, and in urine and plasma aldosterone levels and no change in corticosterone values. Our results confirm, in the intact rat, the antimineralocorticoid action of S characterized by an increase in Na+ excretion but no change in K+ elimination. No inhibitory effect of spironolactone on aldosterone, corticosterone or 18-OH-DOC biosynthesis could be demonstrated in our experimental model.
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000450:Aldosterone / Q000097:blood / Q000652:urine; D000818:Animals; D003345:Corticosterone / Q000652:urine; D004032:Diet; D004039:Diet, Sodium-Restricted; D005243:Feces / Q000032:analysis; D008297:Male; D011188:Potassium / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D013148:Spironolactone / Q000494:pharmacology*
D013148:Spironolactone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D012083:Renin; D011188:Potassium; D003345:Corticosterone