INHIBITORY EFFECT OF CLENTIAZEM (TA-3090), A NEW CALCIUM-ANTAGONIST, ON BALLOON CATHETER-INDUCED INTIMAL THICKENING OF RABBIT AORTA

Male Japanese white rabbits were fed a restricted amount (100 g/head/d ay) of an atherogenic diet containing 40.2% cholesterol and 6% peanut oil during an 8-week experimental period. Atherosclerotic lesions, cha racterized by intimal thickening with lipid deposition, were produced by deendothelialization of the rabbit aorta with a 4 F balloon cathete r halfway through the experiment. Clentiazem (TA-3090), a new calcium antagonist, was administered at an oral dose of 30 mg/kg/day for 4 wee ks starting on the day of deendothelialization. Clentiazem significant ly depressed the intimal thickening without any effect on serum lipid levels. Clentiazem (1, 3, and 10 muM) significantly and dose-dependent ly inhibited the in vitro proliferation of smooth muscle cells that ha d been explanted from the neointima of the deendothelialized aorta. At a higher concentration, this drug markedly inhibited collagen-induced aggregation of rabbit platelets. Diltiazem also showed similar effect s, but the effects of clentiazem were more potent than those of diltia zem. These results suggest that clentiazem exhibits an antiatherogenic effect, at least partly through prevention of smooth muscle cell prol iferation in atheromatous lesions, in addition to its hypotensive acti on.