Endothelin-1 potentiation of angiotensin II stimulation of aldosterone production

Abstract

Endothelin-1 (ET-1) binds to specific receptors in cultured bovine adrenal glomerulosa cells and stimulates aldosterone secretion with a 50% effective concentration (EC50) of 300 +/- 80 pM (mean +/- SE). The relative stimulatory potency for ET-1 is significantly less than that of angiotensin II (ANG II). The incubation of calf zona glomerulosa cells in primary culture with ET-1 and ANG II resulted in a significant potentiation of ANG II effect on aldosterone secretion. The EC50 of ET-1 potentiation of ANG II-induced stimulation of aldosterone secretion was 40 +/- 5 pM (mean +/- SE, n = 4), which is lower than the EC50 for ET-1 stimulation of aldosterone secretion. Adrenocorticotropic hormone (ACTH) stimulation of aldosterone secretion, but not that of potassium, was also potentiated by ET-1, but to a lesser degree. ET-1 and ET-1-mediated potentiation of ANG II-stimulated aldosterone biosynthesis increased both the early and late pathways of aldosterone biosynthesis, but the potentiation was greater for the early pathway. Preincubation with ET-1 for at least 15 min, followed by extensive washing to remove bound ET-1, also resulted in persistent potentiation of ANG II-mediated aldosterone secretion. ET-2, sarafotoxin, and vasoactive intestinal contractor potentiation of ANG II action were very similar to that of ET-1. ET-3 and Big-ET-1 potentiated ANG II stimulation only at the highest doses tested and the proendothelin-(110-130) fragment was inactive. ET-1 potentiation of ANG II action is likely to be mediated through an ETB receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)