Nifedipine and Vascular Smooth Muscle Cells in Atherogenesis: In Vivo and In Vitro Studies
Several calcium antagonists have been reported to be effective antiatherogenic agents . Among the calcium antagonists, nifedipine is the foremost and perhaps the most widely studied drug. In experimental animals  as well as in humans , nifedipine has been found to prevent the development of newly formed lesions and/or the progression of preexisting atherornas. Some conflicting findings regarding the efficacy of nifedipine and other calcium antagonists [1,4] in preventing experimental atherosclerosis are likely to be due to differences in the experimental conditions, the species or breed of animals used, or the method employed for assessing atherosclerosis. On the whole, the results of the majority of studies are consistent with the assumption of an appreciable antiatherogenic effect of at least three calcium antagonists, namely nifedipine, verapamil, and isradipine , and indicate that calcium antagonists promise well for clinical use in this field also. Never- theless, the mechanism or mechanisms by which calcium antagonists may exert their antiatherogenic effect remains poorly understood. Since it is presently well accepted that vascular smooth muscle cells (SMC) are the major contributor to the formation of atherosclerotic plaque , we have studied SMC composition in the intimai thickening of hypercholesterolemic rabbits treated with nifedipine. A panel of monoclonal antimyosin antibodies was used to study SMC differentiation during atherogenesis and nifedipine treatment. These antibodies were directed against smooth-muscle or nonmuscie myosin isoforms . This approach allowed the identification of different SMC populations in the aortic wall and enabled us to define their modulation during atherogenesis. We also studied the influence of nifedipine on growth rate and incorporation of [3H]thymidine in SMC cultured from the aortic media.
KeywordsVascular Smooth Muscle Cell Calcium Antagonist Myosin Heavy Chain Rabbit Aorta Antiatherogenic Effect
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