The role of thromboxane (TX) A2 in rabbit arterial thrombosis induced by endothelial damage.
To clarify the role of thromboxane (TX) A2 in arterial thrombus formation, we examined the antithrombotic effects of both a TXA2 synthetase inhibitor (CV-4151) and a TXA2 receptor antagonist (AA-2414) on the rabbit common carotid artery thrombosis which was induced by injury of the endothelium by treatment with 0.25% pronase solution. CV-4151 (1,10 mg/kg, p.o.) and AA-2414 (10 mg/kg, p.o.) significantly inhibited thrombus formation. Furthermore, the combined use of CV-4151 and AA-2414 (0.1 mg/kg, p.o. each) significantly inhibited thrombus formation, though these drugs at the same doses had no effect when administered singly. The plasma level of 11-dehydro TXB2 increased significantly during thrombus formation, and CV-4151 (10 mg/kg) markedly inhibited this increase. There was a significant correlation between the in vivo antithrombotic effects of these drugs and their ex vivo inhibitory effects on arachidonic acid-induced platelet aggregation. The antithrombotic effect of CV-4151 also correlated significantly with its ability to inhibit the production of serum TXA2. These results show that TXA2 may play an important role in the thrombus formation in arterial thrombosis.
Imura
Y
Y
Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Terashita
Z
Z
Nishikawa
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D016227:Benzoquinones; D002341:Carotid Artery Thrombosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006538:Heptanoic Acids; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology; D011817:Rabbits; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D016227:Benzoquinones; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D011725:Pyridines; D011809:Quinones; D016718:Arachidonic Acid; C060230:seratrodast; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C049235:11-dehydro-thromboxane B2; D013930:Thromboxane-A Synthase; C045446:isbogrel