Reduced platelet aggregation by effects of pentoxifylline on vascular prostacyclin isomerase and platelet cyclic AMP.

1. Inhibition of platelet aggregation in vitro by pentoxifylline is rather weak, requiring about 1 mM pentoxifylline. Ex vivo, however, 15 mg/kg p.o. pentoxifylline exerts an enhanced release of prostacyclin-(PGI2)-like antiaggregatory activity from rat aortas. 2. Rat aorta incubated in vitro with 1 microM pentoxifylline releases antiaggregatory activity in a similar manner. The conversion of prostaglandin H2 to PGI2-like activity which is catalyzed by vascular microsomes, also is drastically stimulated in vitro by addition of 1 microM pentoxifylline. 3. Despite its inhibitory effect on platelet cyclic AMP-phosphodiesterase pentoxifylline in vitro without PGI2 has no essential effect on cyclic AMP levels in human platelets. However, in presence of PGI2, release of which probably is increased by pentoxifylline cyclic AMP level as well as inhibition of aggregation are enhanced by pentoxifylline above the effects of PGI2 itself.