A study of the stimulation of human venous prostacyclin synthesis by dipyridamole

The synthesis of prostacyclin by human venous tissue in vitro and the effects of aspirin and dipyridamole thereon were investigated. Dipyridamole significantly stimulated prostacyclin production in a concentration range of 25 to 100 microM. Dipyridamole significantly attenuated the inhibitory effect of 0.1 mM aspirin in a concentration range of 12.5 to 100 microM. Isobutylmethylxanthine 0.1 mM, an unrelated inhibitor of phosphodiesterase, had similar effects to dipyridamole. Cyclic AMP 3.0 mM had an inhibitory effect on prostacyclin synthesis in the presence of dipyridamole. Adenosine 0.1 mM and nitrobenzylthioguanosine 0.1 mM, an inhibitor of adenosine uptake, did not significantly influence prostacyclin synthesis in this system. We conclude that the stimulation of prostacyclin synthesis by dipyridamole is unrelated to the ability of this drug to block the high-affinity uptake of adenosine by endothelial cells and that the effect may also be independent of changes in the concentration of cAMP induced by the drug.