The antiatherosclerotic effects of calcium antagonists

It has been known for some time that calcium antagonists demonstrate antiatherosclerotic activity. These agents have been shown to reduce the extension of atherosclerotic lesions in cholesterol-fed rabbits without affecting plasma lipid concentrations or blood pressure, suggesting a direct protective effect on the arterial wall. Lacidipine is a recently developed dihydropyridine calcium antagonist that is extremely lipophilic and has potent and long-lasting antihypertensive properties. Lacidipine directly inhibits the enzyme, acylcoenzyme A-cholesterol acyltransferase, and affects intracellular cholesterol homeostasis by preventing acetyl low-density lipoprotein cholesterol esterification. In vivo studies have shown that lacidipine also reduces the intimal hyperplasia induced by insertion of a plastic collar around one carotid artery in cholesterol-fed rabbits. In animals treated with lacidipine, the rapid proliferation of smooth-muscle cells inside the carotid wall is totally inhibited. Lacidipine, therefore, appears to protect the arterial wall against the development of atherosclerotic lesions in animal or human subjects with severe and multiple risk factors. It seems likely that these effects are achieved by a direct action on the mechanisms involved in atherogenesis.