A nifedipine-sensitive smooth muscle cell population is present in the atherosclerotic rabbit aorta

Abstract

We evaluated the ability of the Ca2+ channel blocker nifedipine to influence the severity of atherosclerotic lesions and the pattern of aortic smooth muscle cell (SMC) differentiation in cholesterol-fed New Zealand White rabbits. The animals were fed a 1% cholesterol-enriched diet for 12 weeks. After 4 weeks of the diet, some rabbits were given nifedipine (20 mg b.i.d.) for another 8 weeks without discontinuation of the cholesterol-enriched diet (experiment 1). Another group of rabbits was treated with nifedipine from the beginning of the cholesterol-enriched diet for the entire 12 weeks (experiment 2). The severity of ahterosclerotic lesions was determined by computerized planimetry, and qualitative effects of nifedipine on SMCs were studied by monoclonal antibodies specific for smooth muscle and nonmuscle myosins. In the aortic media of normal rabbits, these antibodies can identify an SMC population with an "immature" type of myosin pattern; a marked increase in the number of these cells is observed during atherogenesis. In experiment 1, we observed a marked decrease of medial SMCs with the immature type of myosin pattern, without any significant reduction in atherosclerosis severity. In experiment 2, disappearance of the previously mentioned medial SMC population was accompanied by a dramatic slowing of intimal lesion development. These results indicate that nifedipine treatment is effective in reducing atherosclerotic lesions only when given from the beginning of a cholesterol-enriched diet. Delay of nifedipine administration until the fourth week of the cholesterol-enriched diet fails to halt progression of the disease. The observed antiatherosclerotic activity can be attributable to a direct effect of the drug on the medial SMC population, which increases during the course of experimental atherogenesis.