The effects of canrenoate K on corticosteroid biosynthesis in nephrectomized dogs.
There is evidence from in vitro experiments that spironolactone not only antagonises the peripheral effects of aldosterone but also inhibits the production of corticosteroids by the adrenals. However relevant data from clinical studies are contradictory probably because spironolactone action on the kidneys also activates other mechanisms, such as renin secretion and potassium retention, which are potent stimulants of the adrenal cortex and thus tend to compensate for the inhibition. To determine the inhibitory effect of spironolactone on the adrenals in isolation, three groups of nephrectomized dogs were studied. Steroidogenesis was stimulated either by angiotensin II, potassium, or ACTH infusion. Potassium canrenoate was administered i.v. bolus at the beginning of the experiment. All the groups showed a similar marked decrease in plasma renin activity (PRA). Plasma aldosterone and cortisol were stimulated by the appropriate stimulus but their increase was blunted after the canrenoate K administration. The altered response between the subgroups was statistically significant (P less than 0.05). Plasma progesterone increased after the administration of canrenoate K. The response difference between the respective subgroups was again statistically significant (P less than 0.05). Canrenoate K was rapidly eliminated from the systemic circulation. These data indicate that canrenoate K causes a partial inhibition of aldosterone and cortisol stimulated secretion but augments the plasma levels of the precursor progesterone, as would be expected following inhibition of specific steps of corticosteroid biosynthesis.
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002191:Canrenoic Acid / Q000097:blood / Q000494:pharmacology*; D004285:Dogs; D006854:Hydrocortisone / Q000097:blood; D066298:In Vitro Techniques; D007700:Kinetics; D009392:Nephrectomy; D011245:Pregnadienes / Q000494:pharmacology*; D012083:Renin / Q000097:blood
D000305:Adrenal Cortex Hormones; D011245:Pregnadienes; D000804:Angiotensin II; D000450:Aldosterone; D002191:Canrenoic Acid; D000324:Adrenocorticotropic Hormone; D012083:Renin; D006854:Hydrocortisone