Carvedilol inhibits basal and stimulated ACE production in human endothelial cells

Angiotensin-converting enzyme (ACE) plays an important role in the pathophysiology of cardiovascular disease. We examined the effect of carvedilol, a cardiovascular drug, on basal and stimulated ACE production in human endothelial cells. Carvedilol (0.625-5 muM), in a concentration-dependent manner, inhibited basal and vascular endothelial growth factor (VEGF, 0.5 nM) or phorbol 12-myristate 13 -acetate (PMA, 10 nM) induced ACE up-regulation. Carvedilol has non-selective beta-adrenoceptor and selective alpha 1-adrenoceptor blocking activity, calcium channel blocking, and antioxidant activity. To study whether these activities were related to ACE down-regulation, endothelial cells were treated with metoprolol (1-10 muM), propranolol (1-10 muM), prazosin (1-5 muM), nicardipine (1-10 muM), probucol (1-100 muM), or ascorbic acid (1-100 muM). None of these compounds modified ACE. VEGF (0.5 nM) and PMA (10 nM) induced PKC phosphorylation, which was inhibited by co-treatment of cell cultures with carvedilol (5 muM). In conclusion, carvedilol inhibited basal and VEGF or PMA induced ACE up-regulation. Inhibition of PKC phosphorylation was probably involved in carvedilol action.