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 microM), 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 alpha1-adrenoceptor blocking activity, calcium channel blocking, and anti-oxidant activity. To study whether these activities were related to ACE down-regulation, endothelial cells were treated with metoprolol (1-10 microM), propranolol (1-10 microM), prazosin (1-5 microM), nicardipine (1-10 microM), probucol (1-100 microM), or ascorbic acid (1-100 microM). 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 microM). In conclusion, carvedilol inhibited basal and VEGF or PMA induced ACE up-regulation. Inhibition of PKC phosphorylation was probably involved in carvedilol action.

Citation

Outi Saijonmaa, Tuulikki Nyman, Frej Fyhrquist. Carvedilol inhibits basal and stimulated ACE production in human endothelial cells. Journal of cardiovascular pharmacology. 2004 May;43(5):616-21

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PMID: 15071347

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