Endothelin-1 stimulates arginine-vasopressin and atrial natriuretic peptide release by rat adrenal medulla: receptor subtypes involved and possible functional relevance

Arginine-vasopressin (AVP) and atrial natriuretic peptide (ANP) are contained in adrenal medulla and are thought to control aldosterone secretion by the zona glomerulosa in a paracrine manner. Endothelin-1 (ET-1), a potent aldosterone secretagogue, can enhance AVP and ANP release by rat hypothalamo-neurohypophyseal axis and atrial cardiocytes respectively. Hence, we have investigated the effects of ET-I on AVP and ANP release by rat adrenal medulla fragments in vitro. Radioimmunoassay showed that ET-1 enhanced AVP-immunoreactivity (ir) release in a concentration-dependent manner, minimal and maximal effective concentrations being 10(-9) and 10(-7) M, respectively. The effect of ET-1 on ANP-ir release was less intense and significant only at a peptide concentration of 10(-8)/10(-7) M. The secretagogue effects of ET-1 (10(-7) M) were annulled by ETA-receptor antagonist BQ-123 (5 x 10(-7) M), and unaffected by the ETB-receptor antagonist BQ-788 ET-1 (10(-7) M) evoked a marked rise in aldosterone secretion of rat adrenal slices. This effect of ET-1 was slightly but significantly counteracted by an antagonist of AVP, but not of ANP receptors. Collectively, these findings allow us to conclude that: (1) ET-1 stimulates rat adrenal medulla secretion of both AVP and ANP, exclusively acting via the ETA-receptor subtype; and (2) the ETA receptor-mediated release of AVP, but not of ANP may play a role in the aldosterone secretagogue effect of ET-1. Med Sci Res 27:163-165 (C) 1999 Lippincott Williams & Wilkins.