Effect of dipyridamole on prostaglandin generation by human platelets and vessel walls.
These experiments were conducted to determine the effects of dipyridamole on human platelet aggregation, platelet thromboxane A2 (TXA2) and human vessel wall prostacyclin (PGI2) generation. Dipyridamole in varying concentrations (5 to 50 micrograms/ml) had no direct effect on ADP-induced platelet aggregation in vitro, but it potentiated PGI2-induced platelet aggregation inhibition at these concentrations. Dipyridamole also inhibited arachidonic acid-induced platelet TXA2 generation at these concentrations. In continuously perfused umbilical vein segments, dipyridamole treatment resulted in stimulation of PGI2 release determined by bioassay and by measurement of its stable metabolite 6-keto-PGF1 alpha. Minimum concentration of dipyridamole causing PGI2 release was 50 micrograms/ml. These in vitro studies suggest that anti-thrombotic effects of dipyridamole in man are mediated mainly by potentiation of PGI2 activity and to some extent by TXA2 suppression. Stimulation of PGI2 release by human vessels may not be seen in usual therapeutic concentrations.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology*; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D011453:Prostaglandins; D013931:Thromboxanes; D016718:Arachidonic Acid; D013928:Thromboxane A2; D004176:Dipyridamole; D011464:Epoprostenol