Aspirin inhibits the synthesis of both platelet and vascular arachidonic acid metabolites which have opposite effects on platelet function. The rationale for its clinical use as an antithrombotic drug has therefore been questioned. Previous studies in rats indicated that platelets are more sensitive to aspirin than arterial tissues and are almost as sensitive as venous tissues. We have now assessed the effects of aspirin at various doses on an arterial and a venous model of experimentally-induced thrombosis. Aspirin at high doses (50-200 mg/kg b.w.) neither reduced nor potentiated the thrombosis tendency in either model. Lower doses (2.5-10 mg/kg b.w.) - which preferentially inhibited platelet prostaglandin formation - did not protect the animals against thrombosis. It is possible, on one hand, that the metabolic pathways of arachidonic acid which are blocked by aspirin do not play a crucial role in the models used. One the other hand, the difficulty to completely dissociate the inhibitory effects of aspirin on platelet and vascular prostaglandins could be crucial for the antithrombotic activity of this drug. The concept that, when administered in large doses, aspirin - by inhibiting vascular prostacyclin activity - potentiates experimental thrombosis, is not supported by the present study.
- Experimental thrombosis
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine