EVIDENCE THAT BOTH ET(A) AND ET(B) RECEPTOR SUBTYPES ARE INVOLVED IN THE IN-VIVO ALDOSTERONE SECRETAGOGUE EFFECT OF ENDOTHELIN-1 IN RATS

Endothelins (ET) are a family of vasoconstrictor peptides, secreted by vascular endothelium, which act through two main subtypes of receptor s: ET(A) and ET(B). ET-1 is known to stimulate aldosterone (ALDO) secr etion by adrenal zona glomerulosa (ZG), and in vitro its effect was re cently found to be exclusively mediated by ET(B) receptors. In this st udy the involvement of ET(A) and ET(B) in the mediation of the in vivo acute ALDO secretagogue action of ET-1 was investigated by the use of their selective antagonists BQ-123 and BQ-788, respectively. The bolu s intraperitoneal administration of ET-1 dose-dependently raised both basal and angiotensin II (ANG II)-enhanced plasma ALDO concentration ( PAC) in rats. Both antagonists counteracted the stimulatory effect of ET-1 on basal PAC, and when administered together completely annulled it. Conversely, only BQ-788 reversed the effect of ET-1 on ANG II-enha nced PAC. ET-1 increased systolic blood pressure (BP) in normal rats, but not in animals simultaneously administered ANG II. The hypertensiv e effect of ET-1 was completely abolished by BQ-123, and not affected by BQ-788. In light of these findings the following conclusions can be drawn: (i) the in vivo ALDO secretagogue action of ET-1 is mediated b y both ET(A) and ET(B), this latter subtype of ET receptors playing a major role; and (ii) the mechanism whereby ET(A) participates in this in vivo effect of ET-1 is indirect, and probably connected with the ET -1-induced rise in BP and adrenal blood flow.