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A direct effect of aldosterone on endothelin-1 gene expression in vivo.

Authors :
Wong S
Brennan FE
Young MJ
Fuller PJ
Cole TJ
Source :
Endocrinology [Endocrinology] 2007 Apr; Vol. 148 (4), pp. 1511-7. Date of Electronic Publication: 2007 Jan 11.
Publication Year :
2007

Abstract

Aldosterone regulates sodium reabsorption in epithelial tissues such as the kidney and colon, via a pathway involving the activation of intracellular mineralocorticoid receptors (MR), induction of specific target genes, and a subsequent increase in sodium channel activity. Characterized aldosterone target genes in epithelia include the serum and glucocorticoid-regulated kinase 1 and the corticosteroid hormone-induced factor. Endothelin-1 (ET-1) is a potent vasoconstrictor that alters both sodium transport and hydrogen ion secretion in the kidney. Recent studies in a mouse medullary collecting duct cell line and rat A-10 smooth muscle cells have demonstrated an acute response of ET-1 gene expression to aldosterone. In the present study, we have investigated the ET-1 gene in vivo as a potential direct aldosterone-regulated target gene in the kidney and colon. Adrenalectomized rats given a single dose of aldosterone were found to have a 2-fold increase in ET-1 mRNA levels in the kidney and colon after 1 h. No significant changes in mRNA levels were detected for the related isoforms ET-2 or ET-3. Cotreatment with aldosterone and potassium canrenoate, a MR antagonist, blocked induction of ET-1 mRNA, suggesting that induction was mediated via the MR. In a time course study, ET-1 mRNA levels were induced rapidly by aldosterone, with levels of ET-1 mRNA maximally increased 2- and 2.5-fold after 1 h in the kidney and colon, respectively. These results suggest that ET-1 is a direct aldosterone gene target in the kidney and colon and may play an important role in aldosterone-regulated ion homeostasis.

Details

Language :
English
ISSN :
0013-7227
Volume :
148
Issue :
4
Database :
MEDLINE
Journal :
Endocrinology
Publication Type :
Academic Journal
Accession number :
17218419
Full Text :
https://doi.org/10.1210/en.2006-0965