Dipyridamole and aspirin in relation to platelet aggregation and vessel wall prostaglandin generation.
Modification of platelet function and vessel wall prostaglandin synthesis by pharmacologic intervention has attracted considerable attention. We report our observations on the effects of aspirin and dipyridamole alone and their combination on platelet aggregation and vessel wall prostacyclin (PGI2) generation. Although dipyridamole alone had no effects on platelet aggregation, it potentiated the platelet aggregation inhibitory effects of aspirin in vitro in a dose-related fashion. Dipyridamole also enhanced the platelet aggregation inhibitory effect of synthetic PGI2 in vitro. Potentiation of aspirin- and PGI2-induced platelet aggregation inhibition was observed in therapeutic range (5-10 micrograms/ml). In an isolated umbilical vein model dipyridamole stimulated release of PGI2 at much higher concentration (50-100 microgram/ml). Treatment of umbilical vein with aspirin (180 micrograms/ml) for 10 min blocked the spontaneous release of PGI2. In aspirin-treated umbilical vein segments dipyridamole treatment did not cause PGI2 release as in the untreated segments. These experiments suggest that although dipyridamole enhances both aspirin- and PGI2-induced platelet aggregation inhibition in clinically achieved concentrations, much higher levels are necessary for PGI2 release from intact human vessels. Furthermore, aspirin treatment of human vessels may prevent release of PGI2 in response to dipyridamole by blocking cyclooxygenase enzyme.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D001241:Aspirin / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000378:metabolism
D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin; D004837:Epinephrine