Glucocorticoid regulation of angiotensin-converting enzyme in primary culture of adult cardiac fibroblasts

Abstract

The effect of dexamethasone on angiotensin-converting enzyme (ACE) in primary culture of adult cardiac fibroblasts was analyzed in this study. ACE is central to cardiac remodeling in conditions such as myocardial infarction (MI). Some studies indicate that glucocorticoids are often increased post-MI, whereas other studies suggest that glucocorticoids stimulate ACE activity in various cell types. Most cardiac cells are fibroblasts, which have an important function in cardiac remodeling. Therefore, we studied the effects of glucocorticoids on ACE activity and mRNA levels in primary cultures of adult rat cardiac fibroblasts. Steady-state ACE activity was very low, but it increased sixfold with dexamethasone (1 μM for 48 h) treatment. ACE activation occurred within 12 h and peaked at 96 h, after treatment. RNase-protection assays revealed an associated threefold increase ( P < 0.05) in ACE mRNA. Dexamethasone's stimulatory effect was abolished by an RNA synthesis inhibitor (actinomycin D, 5 μg/ml) but was potentiated by a protein synthesis inhibitor (cycloheximide, 5 μg/ml). The glucocorticoid-mediated response appears to be specific, because mineralocorticoid treatment did not alter ACE activity. These findings indicate that both transcriptional and posttranscriptional mechanisms are involved in glucocorticoid regulation of ACE expression in rat cardiac fibroblasts.