Aldosterone stimulates angiotensin-converting enzyme expression and activity in rat neonatal cardiac myocytes.
BACKGROUND
Members of the nuclear receptor family proteins function as transcription factors upon ligand binding and thereby regulate gene expression in host cells. Aldosterone, the high-affinity endogenous ligand for the mineralocorticoid receptor, induces cardiac hypertrophy and fibrosis in a variety of animal models, but the transcriptional targets for aldosterone in the myocardium are not well-described.


RESULTS
Using quantitative reverse transcription-polymerase chain reaction method, we show that in cultured rat neonatal cardiomyocytes, aldosterone stimulates expression of angiotensin converting enzyme (ACE) in a concentration and time-dependent manner. Aldosterone (50 and 100 nM) increased levels of ACE mRNA by 1.8- and 2.2-fold, respectively. Aldosterone-induced ACE gene expression was blocked by spironolactone (1 microM), a mineralocorticoid receptor antagonist. In contrast, the expressions of the type I angiotensin receptor was not induced by aldosterone in either cardiac myocytes or fibroblasts. Consistent with the increased ACE mRNA level, 100 nM aldosterone also induced a 2-fold increase in ACE activity in cardiac myocytes.


CONCLUSIONS
ACE gene expression may be a target for mineralocorticoid receptors in the myocardium, supporting the notion that at least some of the known adverse effects of aldosterone on the myocardium are mediated by increased angiotensin II.
Wang
Jian
J
Cardiovascular Research, Lilly Research Laboratory, Indianapolis, Indiana 46285, USA.
Yu
Lan
L
Solenberg
Patricia J
PJ
Gelbert
Lawrence
L
Geringer
Chad D
CD
Steinberg
Mitchell I
MI
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D023421:Models, Animal; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A