title: Carvedilol inhibits basal and stimulated ACE production in human endothelial cells.
abstract: 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.
authors.affiliation: Minerva Institute for Medical Research, Helsinki, Finland. outi.saijonmaa@helsinki.fi
authors.forename: Outi
authors.initials: O
authors.lastname: Saijonmaa
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Nyman
authors.forename: Frej
authors.initials: F
authors.lastname: Fyhrquist
mesh_terms: D002227:Carbazoles / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D000077261:Carvedilol; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011412:Propanolamines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002227:Carbazoles; D002317:Cardiovascular Agents; D011412:Propanolamines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D000077261:Carvedilol; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D011493:Protein Kinase C; D007703:Peptidyl-Dipeptidase A; D013755:Tetradecanoylphorbol Acetate