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Synergistic stimulation of aldosterone production in human adrenocortical carcinoma NCI-H295R cells by endothelin-1 and angiotensin II.

Hu, Chii-Whei and Webb, Randy and Jeng, Arco (2004) Synergistic stimulation of aldosterone production in human adrenocortical carcinoma NCI-H295R cells by endothelin-1 and angiotensin II. Journal of Cardiovascular Pharmacology, 44 Suppl 1. S289-S292. ISSN 1533-4023

Abstract

Aldosterone has recently been implicated in the pathogenesis of heart failure. The purpose of the present study was to determine the effect of endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictors that are also involved in heart failure, on aldosterone secretion by human adrenocortical carcinoma NCIH295R cells grown in 96-well plates. Ang II stimulated the production of aldosterone dose-dependently in serum-free medium, and the presence of serum drastically decreased aldosterone secretion. In contrast, ET-1-stimulated aldosterone production absolutely required serum. Under optimal conditions, ET-1 was more effective than Ang II as an aldosterone secretagogue. In a suboptimal condition of 2.5% serum, ET-1 and Ang II at 1 microM produced 63 and 76 pmol aldosterone/mg protein, respectively, while 230 pmol aldosterone/mg protein was generated upon coincubation with ET-1 and Ang II. The effect of ET-1 was inhibited dose-dependently by the selective ETA receptor antagonist BQ-123 with an IC50 of 23 nM, but the selective ETB receptor antagonist RES-701 had no effect up to 10 microM. These results suggest that ET-1 and Ang II stimulated aldosterone secretion synergistically in NCIH295R cells and that the effect of ET-1 was mediated via the ETA receptor subtype.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 13:56
Last Modified: 14 Dec 2009 13:56
URI: https://oak.novartis.com/id/eprint/646

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