Aldosterone stimulates angiotensin-converting enzyme expression and activity in rat neonatal cardiac myocytes

• Published in: Journal of cardiac failure Vol. 8; no. 3; pp. 167 - 174
• Main Authors: Wang, Jian, Yu, Lan, Solenberg, Patricia J., Gelbert, Lawrence, Geringer, Chad D., Steinberg, Mitchell I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2002
• Subjects: Aldosterone - pharmacology; angiotensin; Animals; Cells, Cultured; Gene Expression - drug effects; mineralocorticoid receptor; Models, Animal; Myocardium - cytology; Myocardium - enzymology; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; quantitative RT-PCR; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; angiotensin; quantitative RT-PCR; mineralocorticoid receptor
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1054/jcaf.2002.125369

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. Methods and 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 μM), 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. Conclusion: 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.