title: A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea pigs.
abstract: 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
authors.affiliation: Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: M
authors.initials: M
authors.lastname: Shimazawa
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
mesh_terms: 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
chemical_list: D005343:Fibrinolytic Agents; D014841:von Willebrand Factor; D001312:Aurintricarboxylic Acid; D003094:Collagen