The Inhibitory Effect of Aspirin on Platelet and Vascular Prostaglandins in Rats cannot be Completely Dissociated

Abstract

S ummary . Blood platelets and vascular endothelium generate prostaglandin derivatives with opposing effects: cyclic endoperoxides and thromboxane A 2 (TXA 2 ) aggregate platelets, whereas prostaglandin I 2 (PGI 2 , prostacyclin) inhibits aggregation. Since aspirin inhibits the synthesis and effects of all these metabolites of arachidonic acid, the rationale for clinical use of this drug in thrombosis prevention trials is questionable. Treatment schedules would have to be calibrated to inhibit proaggregating platelet prostaglandins and TXA 2 without affecting protective vascular prostaglandins (PGI 2 ). This important clinical information cannot easily be obtained from studies in man. The present study indicates that normal rat platelets are more sensitive to aspirin (ID 50 =3.6 mg/kg) than arterial tissues (ID 50 =25.0 mg/kg) and are almost as sensitive as venous tissues (ID 50 =2.3 mg/kg). Platelet prostaglandin production was monitored through the measurement of malondialdehyde (MDA) output under standard stimulation with thrombin. PGI 2 ‐like activity released from the abdominal aorta and inferior vena cava was determined as platelet aggregation inhibitory potency and characterized by standard criteria. The inhibitory effect of aspirin (at doses of 10 and 50 mg/kg) on platelet MDA production lasted much longer in platelets (96–120 h) than in venous (24–72 h) or arterial tissue (less than 24 h). The findings suggest that in rats the (potentially antithrombotic) effect of aspirin on platelet prostaglandin and TXA 2 generation may be distinguished, though not completely, from the (potentially prothrombotic) effect on vascular PGI 2 on the basis of duration of inhibition more than on the sensitivity of the target cells to the drug. The different capacities of anucleated platelets and of nucleated vascular endothelial cells to overcome aspirin inhibition could be exploited for more rational clinical use of this drug.