A direct effect of aldosterone on endothelin-1 gene expression in vivo.
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.
Wong
Stephen
S
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Brennan
Francine E
FE
Young
Morag J
MJ
Fuller
Peter J
PJ
Cole
Timothy J
TJ
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D019333:Endothelin-2 / Q000378:metabolism; D019334:Endothelin-3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone