Z-335, a Thromboxane A2 Receptor Antagonist, Suppresses the Progression of Arachidonic Acid-Induced Hind Limb Gangrene in Rats.
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Abstract
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.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 22 (12), 1382-1384, 1999
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204624412544
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- NII Article ID
- 110003639614
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 4938482
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- PubMed
- 10746175
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed