A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea pigs.
1. The antithrombotic effect of aurintricarboxylic acid (ATA) which inhibits binding of von Willebrand factor (vWF) to platelet glycoprotein lb (GPlb) receptor was evaluated in photochemically-induced thrombosis models in the femoral artery of rats and guinea-pigs. 2. ATA at a dose of 10 mg kg-1 significantly prolonged the time required for thrombotic occlusion of the artery in rats. The antithrombotic efficacy was associated with a significant inhibition of platelet retention and ex vivo botrocetin-induced platelet aggregation. 3. On the other hand, in guinea-pigs, ATA at the same dose inhibited the platelet retention and the platelet aggregation, but did not prevent thromboocclusion. 4. ATA inhibited aggregation of washed platelets from rats or guinea-pigs in response to botrocetin and thrombin in a dose-dependent manner (1-30 microM), and to the same extent. 5. ATA moderately increased activated partial thromboplastin time and bleeding time in both species. 6. These results indicate that vWF may play a role in the development of occlusive arterial thrombosis in the rat, but not in the guinea-pig. 7. The antithrombotic activity of ATA may partly arise from its inhibitory effect on thrombin, in addition to that on the vWF-GPlb pathway
Takiguchi
Y
Y
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Shimazawa
M
M
Nakashima
M
M
D000818:Animals; D001312:Aurintricarboxylic Acid / Q000627:therapeutic use*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D005263:Femoral Artery / Q000473:pathology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006168:Guinea Pigs; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors
D005343:Fibrinolytic Agents; D014841:von Willebrand Factor; D001312:Aurintricarboxylic Acid; D003094:Collagen