Role of mineralocorticoid in the chronic antihypertensive effect of converting enzyme inhibitor.
The chronic antihypertensive effect of converting enzyme inhibtor (CEI) may be due to a decrease in aldosterone secretion secondary to blockade of angiotensin II formation. To study this hypothesis, changes in blood pressure (BP), in response to chronic administration of the CEI, captopril, were measured in spontaneously hypertensive (SHR) and in chronic two-kidney, one clip hypertensive (2K-1C) rats. To avoid a decrease in mineralocorticoid activity, half of the rats in these two models of hypertension were adrenalectomized and maintained with daily administrations of deoxycorticosterone acetate and hydrocortisone (steroid replacement) while the other half had the adrenal gland left in situ and no exogenous steroids administered. The doses of steroids used were devoid of hypertensive effect in Wistar Kyoto (WKY), SHR, 2K-1C, and sham-clipped rats. Chronic administration of the CEI decreased the BP to normotensive levels in the SHR with intact adrenals and no steroid replacement. However, the antihypertensive effect of the CEI was almost completely blocked in those SHR with steroid replacement. In contrast, the antihypertensive effect of the CEI in 2K-1C was similar in the rats with steroid replacement and in the rats with intact adrenals (no steroid replacement). These results suggest that the chronic antihypertensive effect of CEI in SHR is due partially to a decrease in aldosterone activity secondary to the blockade of angiotensin II formation, whereas in 2K-1C it is due to mechanisms other than lower mineralocorticoid activity.
D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D006854:Hydrocortisone / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D007705:Kinins / Q000494:pharmacology; D008297:Male; D008901:Mineralocorticoids / Q000502:physiology*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D007705:Kinins; D008901:Mineralocorticoids; D003900:Desoxycorticosterone; D011392:Proline; D002216:Captopril; D012083:Renin; D006854:Hydrocortisone