Endothelin-1 potentiation of angiotensin II stimulation of aldosterone production

• Published in: The American journal of physiology Vol. 262; no. 1 Pt 2; p. R85
• Main Authors: Cozza, E N, Chiou, S, Gomez-Sanchez, C E
• Format: Journal Article
• Language: English
• Published: United States 01.01.1992
• Subjects: Adrenocorticotropic Hormone - pharmacology; Aldosterone - biosynthesis; Angiotensin II - pharmacology; Animals; Drug Synergism; Endothelins - pharmacology; Potassium - pharmacology; Time Factors
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpregu.1992.262.1.r85

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.