Dipyridamole Reverses The Inhibitory Effect Of Aspirin On Prostacyclin Synthesis

The value of aspirin (ASA) as an antithrombotic agent is limited by the fact that it inhibits the production of prostacyclin (PGI₂) by the vessel wall. However, there is evidence that the combination of ASA and dipyridamole (DP) has antithrombotic potential for patients with certain types of thrombovascular disease and there appears to be some synergism between the two drugs. To study the relationship between ASA and DP we have examined the effect of the two drugs, singly and in combination on thromboxane (TX) production and PGI₂ synthesis by platelets and vessel walls respectively. Rings of venous tissue prepared from veins obtained during surgery were incubated in Ringers solution with ASA, DP or a combination of both. PGI₂ synthesis was assessed by radioimmunoassay for 6-keto PGF_1α, its stable metabolite on aliquots of supernatant from the incubation mixture during a thirty minute period. All control samples synthesized PGI₂. 0.1mM ASA caused 4299 per cent inhibition of PGI₂. DP at a concentration of 0.05mg/ml had no significant effect on PGI₂ production compared with values obtained in controls. The combination of DP and ASA caused significantly less inhibition of PGI₂ synthesis compared with almost complete inhibition observed with ASA alone.

In similar studies on platelet rich plasma, TXA₂ synthesis, determined by radioimmunoassay for TXB₂, was abolished by ASA 0.15mM, whereas DP 0.05mg/ml had minimal inhibitory action. However, at lower concentrations of ASA the inhibition of both aggregation and TXA₂ synthesis was markedly potentiated by DP 0.05mg/ml.

These results provide an explanation for the reported synergism between ASA and DP.