Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension

Background: Endothelin (ET)-1 contributes to raising blood pressure (BP) and inducing cardiovascular disease by vasoconstriction and potent stimulation of aldosterone secretion. In the rat this latter effect occurs via ET,, receptors; in humans in vitro studies implicated both ETA and ETB receptors, but there is no conclusive evidence in vivo. Methods: We recruited 13 consenting hypertensive patients: six with primary aldosteronism (PA) and seven with high-to-normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min for 5 min followed by 100 nmol/min for 10 min) of the ETA-selective antagonist BQ-123 either alone or, on a different day, together with an identical dose of the ETB-selective antagonist BQ-788. Plasma alosterone, cortisol and ACTH concentration and plasma renin activity (PRA) were measured with radioimmunoassay at - 15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively. Results: BQ-123 alone and combined with BQ-788 significantly lowered mean BP in both PA and HNRH patients (by 6-10 mmHg at nadir; P<0.01). In PA patients, a short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (-14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788 lowered aldosterone (-39 and -28%, respectively) and PRA (-43 and - 16%, respectively), while cortisol and ACTH were unaffected. Conclusions: Endogenous ET-1 contributes to maintaining the high BP values and the aldosterone secretion in both PA and HNRH patients. In the former patients, the aldosterone secretagogue effect of ET-1 is mediated via ETB receptors, while in the latter it occurs mainly via ETA -mediated stimulation of renin production. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.