ANTIATHEROGENIC ACTION OF NITRENDIPINE IN HYPERCHOLESTEROLEMIC RABBITS - CHANGES IN AORTIC MACROPHAGE ACCUMULATION AND SMOOTH-MUSCLE CELL PHENOTYPE

Intimal accumulation of macrophages and changes in the phenotype and g rowth properties of vascular smooth muscle cells (SMCs) represent key events in the development of atherosclerotic lesions. Here we report o n the in vivo effect exerted by nitrendipine on aortic tissue of chole sterol-fed rabbits. We have focused especially on the myosin heavy cha in (MyHC) pattern expressed by aortic SMC, taken as a marker of cell d ifferentiation. Using monoclonal antibodies specific to the different forms of MyHC, three differentiation steps were determined: adult, pos tnatal, and fetal. Nitrendipine administered in conjunction with a cho lesterol-enriched diet reduced the development of atherosclerotic lesi ons (atherosclerosis index: 0.21 vs. 0.32 in untreated animals, p < 0. 005), despite persistently high serum cholesterol levels. Compared to untreated controls, nitrendipine-treated animals displayed a decreased number of postnatal-type SMCs in the media underlying the plaque (pre valence index: 0.07 vs. 0.26, p < 0.0001 and a lower aortic cholestero l content (free cholesterol: 3.3 vs. 11.5 ng/mg, p < 0.0001; esterifie d cholesterol: 7.2 vs. 40.5 ng/mg, p < 0.0001). Moreover, nitrendipine treatment decreased the intimal accumulation of macrophages and fetal -type SMCs. It is conceivable that calcium antagonists may exert their antiatherogenic effect, at least in part, through cellular changes un related to the classical risk factors.