The calcium-channel blocker lacidipine reduces the development of atherosclerotic lesions in the apoE-deficient mouse

Background Lacidipine is a widely used calcium-channel blocker, which has b oth long-lasting antihypertensive activity and also antioxidant properties. Previous studies have demonstrated the ability of lacidipine to reduce the development of atherosclerotic lesions in several animal models. Objective The present study investigated the antiatherosclerotic potential of lacidipine in the apoE-deficient mouse, an experimental model of atheros clerosis showing progressively complex and widespread lesions which closely resemble the inflammatory-fibrous plaques seen in humans. Methods Lacidipine was administered daily by gavage for in weeks at dose le vels of 0 (control), 0.3, 1.0 and 3.0 mg/kg. Results Lacidipine administration reduces the extension of atherosclerotic lesions in the aorta of the apoE-deficient mouse without affecting plasma l ipid levels. We also show that apoE-deficient mice have four-fold higher va lues of the proatherogenic peptide, endothelin, compared with the wild-type C57BL/6 mouse and that lacidipine administration reduced, in a dose-depend ent manner, the concentrations of plasma endothelin. Conclusion Lacidipine has anti-atherogenic effects in the apoE-deficient mo use, and reduces plasma endothelin concentrations. J Hypertens 18:1429-1436 (C) 2000 Lippincott Williams & Wilkins.