Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig.
The mediators of photochemically induced thrombosis in the femoral artery of guinea pig were investigated. The femoral artery was occluded by a thrombus about 7 min after the initiation of photochemical reaction between rose bengal and green light. Pretreatment with a specific thromboxane (TX) A2 receptor antagonist, vapiprost, a platelet-activating factor (PAF) antagonist, WEB-2086, and ADP-induced platelet aggregation inhibitor, ticlopidine, prolonged the time to occlusion. Within the range of doses used, platelet aggregation in whole blood, which was induced by U-46619, PAF and ADP ex vivo, was inhibited by vapiprost, WEB-2086 and ticlopidine, respectively. In contrast, argatroban, a thrombin inhibitor, had no effect on the time to occlusion, although the dose of argatroban was sufficient to delay the prothrombin time and the activated partial thromboplastin time and to inhibit thrombin-induced platelet aggregation ex vivo. These results suggest that TXA2, PAF and ADP are involved in photochemically induced thrombosis of the guinea pig femoral artery, although the coagulation cascade does not play an important role.
Hirata
Y
Y
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Takiguchi
Y
Y
Wada
K
K
Matsuno
H
H
Umemura
K
K
Uematsu
T
T
Nakashima
M
M
D000244:Adenosine Diphosphate / Q000502:physiology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000502:physiology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013988:Ticlopidine / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D013917:Thrombin; C060013:vapiprost; D013988:Ticlopidine