Reduction in infarct size by chronic amlodipine treatment in cholesterol-fed rabbits

Calcium (Ca)-dependent factors, including cholesterol-induced changes in membrane Ca permeability and Ca deposition into lesions, may contribute to plaque formation and stability during the early and late stages of atherogenesis. Amlodipine can reduce atheroma formation in cholesterol-fed rabbits and may be cardioprotective. We therefore examined the effects of chronic amlodipine treatment (5 mg/kg daily for 10 weeks, p.o.) on infarct size after 30-min coronary occlusion/48-h reperfusion in rabbits fed a diet with or without 1% cholesterol. Infarct size was significantly larger in cholesterol-fed rabbits (72.0 +/- 3.5%, n = 9, mean +/- S.E.M.) than in normal-fed rabbits (47.1 +/- 4.9%, n = 9, P < 0.05). Amlodipine treatment effectively reversed the infarct size augmentation in cholesterol-fed rabbits (46.3 +/- 6.3%, n = 9, P < 0.05), but did not affect infarct size in normal-fed rabbits (51.0 +/- 4.7%, n = 8). In both cholesterol-fed and normal-fed rabbits, Ca content and leukocyte accumulation as assessed by myeloperoxidase activity were significantly higher in the ischemic myocardium than in the nonischemic myocardium. However, Ca content and leukocyte accumulation were markedly elevated in the ischemic myocardium of cholesterol-fed rabbits compared with normal-fed rabbits. Amlodipine treatment effectively reversed this elevation. Acetylcholine showed a marked reduction in endothelium-dependent relaxation in the aorta of cholesterol-fed rabbits, which also was reversed by amlodipine treatment. These results indicate that chronic amlodipine treatment reduces infarct size only in cholesterol-fed rabbits.