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Gian Paolo Rossi, Chiara Ganzaroli, Maurizio Cesari, Andrea Maresca, Mario Plebani, Gastone G. Nussdorfer, Achille C. Pessina, Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension, Cardiovascular Research, Volume 57, Issue 1, January 2003, Pages 277–283, https://doi.org/10.1016/S0008-6363(02)00658-2
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Abstract
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 ETB 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 aldosterone, 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.
