EFFECT OF VARIOUS ANTIPLATELET AGENTS ON ACUTE ARTERIAL THROMBOSIS INTHE RAT

Electrical stimulation of the rat carotid artery causes a deep medial injury and the formation of a platelet-rich thrombus. Occlusive thromb osis at sites of vessel wall injury was significantly reduced after th e oral administration of clopidogrel, a potent analogue of ticlopidine , which showed dose-dependent inhibition of the thrombus formation (ED 50 = 1.0 +/- 0.2 mg/kg, p. o.). Accumulation of thrombotic material wa s also considerably reduced after the i. v. administration of SR 27417 , a highly potent and selective platelet activating factor receptor an tagonist (ED50 = 10 mug/kg, i. v.), nafagrel, a thromboxane A2 synthet ase inhibitor (ED50 = 1.3 mg/kg, i. v.) and hirudin (ED50 = 140 mug/kg , i. v.). A high dose (20 mg/kg, i. v.) of the anti-adhesive tetrapept ide Arg-Gly-Asp-Ser (RGDS) showed only a slight effect on thrombus for mation whereas aspirin was ineffective. These results confirm that ADP and thromboxane A2 play key roles in the initiation and progression o f arterial thrombus formation and suggest that platelet activating fac tor may also modulate thrombosis in this experimental model.