Antiperoxidative actions of calcium antagonists and atherogenesis

Abstract

Recent experimental and clinical studies suggest that structurally disparate calcium channel blockers retard the progression of atherosclerosis. However, mechanisms of action by which calcium blockers exert their antiatherosclerotic effects have not been completely elucidated. Formation of atherosclerotic lesions involves cells (macrophages, endothelial cells, and platelets) not expressing voltage-dependent (L-type) calcium channels, the major drug receptors for calcium channel blockers. Therefore, it is possible that these drugs act by non-L-type channel mechanisms. Recent reports indicate that nifedipine, verapamil, and diltiazem exert antiperoxidative effects on membrane lipids. It has been suggested that antiperoxidants such as probucol and butylated hydroxytoluene (BHT) exert antiatherosclerotic effects by preventing oxidation of low-density lipoprotein (LDL), a modification thought to confer atherogenic properties to the lipoprotein. Therefore, the beneficial effects of calcium channel blockers might be related to their antiperoxidative activity.