Dilazepの実験的粥状硬化症抑制作用とその評価法に関する検討

抄録

Antiatherosclerotic effects of dilazep (Comelian®), which has been widely used in the clinic, were evaluated using cholesterol loaded-rabbits. Hypercholesterolemic control rabbits received only vehicle for 12 weeks, while cholesterol loading had been continued, showed following atherosclerotic features; a), hypercholesterolemia at the levels of of about 2, 000mg/dl, b), increased lipid deposition onto aortic wall, c), thickening in aortic wall. Dilazep given for 12 weeks by s. c. or p. o. administration partially but obviously protected the progression of above mentioned atherosclerotic features except for a). Although the same protective effects were obtained by s. c. administration of aspirin, they were not so clear as s. c. administration of dilazep. The combined administration of dilazep with aspirin both through s. c. and p. o. routes showed the most potent protective effects, namely, antiatherosclerotic effects, whereas a) was scarcely changed under this condition, either. In general, both dilazep and aspirin have been not considered as a hypolipidemic agent. Therefore, it seems to be proper that a) was not changed clearly under any condition tested and the mechanism whereby these drugs exerted antiatherosclerotic effects could be explained from other activities of those than hypolipidemic. As to the pathogenesis of atherosclerotis, the damage of aortic endothelium induced by physical or chemical stress has been widely accepted as one of the causative reactions. On the other hand, it was reported recently that dilazep has a releasing effect of plasminogen activator, which is thought to be located in vascular endothelium, not only in in vitro but also in in vivo experiments. Thus, the investigation on the activity of dilazep against vascular metabolism or function may be necessary to elucidate the mechanism of the antiatherosclerotic effects of dilazep alone or in combination with aspirin. Finally, a few problems about the representation of aortic cholesterol content were discussed.