Inhibitory effect of clopidogrel, vapiprost and argatroban on the middle cerebral artery thrombosis in the rat.
This study investigated the roles of thromboxane A2 (TXA2), ADP and thrombin in middle cerebral artery (MCA) thrombosis in the rat. The rat MCA was occluded by a thrombus induced by the photochemical reaction of rose bengal by green light that causes endothelial damage followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of the photochemical reaction. Vapiprost, a specific TXA2-receptor antagonist; clopidogrel, which has the thienopyridine structure of ticlopidine and is a more potent inhibitor of ADP-induced platelet aggregation than ticlopidine; argatroban, a specific thrombin inhibitor; or heparin was administered intravenously before rose bengal injection. The MCA local blood flow was monitored by a laser Doppler flowmeter. The MCA was occluded by thrombus about 5 min after the initiation of the photochemical reaction. Vapiprost, clopidogrel and argatroban all significantly prolonged the time taken for the thrombotic occlusion of the MCA, but in this respect, heparin was ineffective. Our observations suggest that vapiprost and clopidogrel are useful antithrombotic agents against platelet and fibrin-rich thrombi. The effect of argatroban is attributable to inhibition of thrombin-induced platelet activation and fibrin generation. The thrombosis model described in this study is useful for understanding the mechanism(s) of thrombogenesis in the rat MCA and may be applied to other mammalian species.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Kawai
H
H
Ishihara
H
H
Nakashima
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002536:Cerebral Arteries / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D000077144:Clopidogrel; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010775:Photic Stimulation; D010875:Pipecolic Acids / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides; D013928:Thromboxane A2 / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D001713:Biphenyl Compounds; D005343:Fibrinolytic Agents; D006538:Heptanoic Acids; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013928:Thromboxane A2; D001120:Arginine; D000077144:Clopidogrel; C060013:vapiprost; C031942:argatroban; D013988:Ticlopidine