文章基本信息

标题：Z-335, a Thromboxane A2 Receptor Antagonist, Suppresses the Progression of Arachidonic Acid-Induced Hind Limb Gangrene in Rats
本地全文：下载
作者：Kakao TANAKA ; Yoshihisa FUKUTA ; Youichi FUKUDA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1999
卷号：22
期号：12
页码：1382-1384
DOI：10.1248/bpb.22.1382
出版社：The Pharmaceutical Society of Japan
摘要：We have developed a new rat model of gangrenous peripheral vascular disease with vascular injury and occlusive thrombi. Rat hind limb gangrene was induced by injecting arachidonic acid (2 mg/leg) into the femoral artery. Using this model, we evaluated the effect of a thromboxane A₂ receptor antagonist, Z-335, on the progression of hind limb gangrene. Z-335 (10 mg/kg/d, p.o.) ameliorated arachidonic acid-induced hind limb gangrene. In contrast, daltroban (10 mg/kg/d, p.o.) and cilostazol (100 mg/kg/d, p.o.) tended to improve the hind limb gangrene but their effects failed to reach statistical significance. Z-335 (10 mg/kg. p.o.) inhibited U-46619-induced, but not collagen-induced, platelet aggregation in rat whole blood. Daltroban (10 mg/kg, p.o.) showed a tendency to inhibit U-46619-induced platelet aggregation. Cilostazol (100 mg/kg, p.o.) did not inhibit U-46619- or collageninduced platelet aggregation. Histopathological examination of the injured paws showed that Z-355 (10 mg/kg, p.o.) had partly inhibited the formation of occlusive thrombi. These results indicate that the thromboxane A₂ receptor antagonist Z-335 is effective arachidonic acid-induced hind limb gangrene in rats. Our experiments sugggest that Z-335 may be beneficial in the prevention of gangrenous peripheral vascular disease.
关键词：Z-335;gangrene;peripheral vascular disease;arachidonic acid