Diltiazem Against Sarcolemmal Membrane Lipid Peroxidation

The antiperoxidative activities of nifedipine, verapamil, and diltiazem were compared with that of propranolol by using an in vitro model of sarcolemmal membrane lipid peroxidation. Highly purified sarcolemmal membranes, isolated from canine ventricular myocytes, were peroxidized by a superoxide anion-producing and iron-catalyzed free radical-generating system (dihydroxyfumarate plus FeCI3 and ADP). Lipid peroxidation after 20 minutes of incubation was monitored by malondialdehyde formation. Similar to propranolol, all three calcium blockers exhibited concentration-dependent (10-400 ,M) inhibitory effects against sarcolemmal lipid peroxidation. The order of potency of these agents was nifedipine>propranolol>verapamil> diltiazem. Nifedipine, the most effective calcium blocker, was greater than twofold more potent than propranolol and achieved a significant effect at 10 ,uM. This study suggests that calcium blockers may provide antiperoxidative protection to cardiac membranes. (Circulation Research 1990;66:1449-1452)