IN-VITRO ANTIOXIDANT ACTIVITY OF CALCIUM-ANTAGONISTS AGAINST LDL OXIDATION COMPARED WITH ALPHA-TOCOPHEROL

The dose-dependent (1, 5, 10, 50 mu M) antioxidative activity of calci um antagonists (verapamil, diltiazem, nifedipine, amlodipine, isradipi ne or lacidipine) and alpha-tocopherol against copper-induced LDL (0.2 5 mg/ml) oxidation was compared by measuring the diene formation and t he content of TBARS. For diltiazem no antioxidant effect could be foun d, whereas the other calcium antagonists and a-tocopherol have demonst rated antioxidant activity at least at concentrations of 10 and 50 mu M: alpha-tocopherol > lacidipine > nifedipine > isradipine, verapamil, amlodipine. Additionally, alpha-tocopherol and lacidipine were able t o attenuate LDL-oxidation significantly at 1 and 5 mu M These results indicate in vitro antioxidative activity of calcium antagonists especi ally from the dihydropyridine-type with greatest activity for the stro ngly lipophilic lacidipine. This might be one possible antiatherogenic mechanism of calcium antagonists, since oxidative modification enhanc es the atherogenic potential of LDL. (C) 1994 Academic Inc. Press,