Saso Y, Ohtani A, Odawara A, Iwasaki H, Takashima K, Morita T
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Cardiovasc Drugs Ther. 1993 Apr;7(2):257-64. doi: 10.1007/BF00878516.
Male Japanese white rabbits were fed a restricted amount (100 g/head/day) of an atherogenic diet containing 0.2% cholesterol and 6% peanut oil during an 8-week experimental period. Atherosclerotic lesions, characterized by intimal thickening with lipid deposition, were produced by de-endothelialization of the rabbit aorta with a 4 F balloon catheter halfway through the experiment. Clentiazem (TA-3090), a new calcium antagonist, was administered at an oral dose of 30 mg/kg/day for 4 weeks starting on the day of deendothelialization. Clentiazem significantly depressed the intimal thickening without any effect on serum lipid levels. Clentiazem (1, 3, and 10 microM) significantly and dose-dependently inhibited the in vitro proliferation of smooth muscle cells that had 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 effects, but the effects of clentiazem were more potent than those of diltiazem. These results suggest that clentiazem exhibits an antiatherogenic effect, at least partly through prevention of smooth muscle cell proliferation in atheromatous lesions, in addition to its hypotensive action.
在为期8周的实验期内，给雄性日本白兔喂食限量（100克/只/天）的致动脉粥样化饮食，该饮食含0.2%胆固醇和6%花生油。在实验进行到一半时，用4F球囊导管对兔主动脉进行去内皮处理，从而产生以内膜增厚伴脂质沉积为特征的动脉粥样硬化病变。从去内皮处理当天开始，以30毫克/千克/天的口服剂量给予新型钙拮抗剂克利硫卓（TA - 3090），持续4周。克利硫卓显著抑制内膜增厚，对血脂水平无任何影响。克利硫卓（1、3和10微摩尔）显著且剂量依赖性地抑制从去内皮主动脉新生内膜中分离出的平滑肌细胞的体外增殖。在较高浓度下，该药物显著抑制胶原蛋白诱导的兔血小板聚集。地尔硫卓也表现出类似作用，但克利硫卓的作用比地尔硫卓更强。这些结果表明，克利硫卓除具有降压作用外，至少部分通过预防动脉粥样硬化病变中平滑肌细胞增殖而发挥抗动脉粥样硬化作用。
