Effects of low doses of aspirin and dipyridamole on platelet aggregation in the dog coronary artery.
The circumflex coronary artery of pentobarbital-anesthetized dogs was partially obstructed with an externally applied rigid plastic band. Platelet aggregation at the site of stenosis caused a gradual decline in blood flow in the artery, which was monitored with an electromagnetic flow probe placed proximally to the obstructor. The effects of drugs on platelet aggregation were evaluated by monitoring changes in both the rate and the degree of decline in blood flow. In most dogs, aspirin inhibited intravascular platelet aggregation (ED50 = 1 mg/kg). Dipyridamole, even at doses that severely depressed blood pressure (1 mg/kg), had no effect on platelet aggregation. However, in dogs that had been pretreated with a low dose of dipyridamole (0.2 mg/kg), the antiaggregatory activity of aspirin was enhanced. This potentiation was evident only at low doses of aspirin (0.03 and 0.1 mg/kg), where the drug was 10 times more active; at high aspirin doses, which depressed vascular cyclooxygenase, no potentiation was seen. Further evidence that the mechanism of this synergism may depend on endogenous prostacyclin production at the site of the partial obstruction was seen when cyclooxygenase inhibitors applied topically on the exposed artery eliminated the antiaggregatory effect of low doses of aspirin. It is important to note that the protective effect of dipyridamole and low-dose aspirin was less than that seen at the high doses of aspirin alone, suggesting that the theoretical benefits of platelet-specific doses of aspirin may be overstated.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D003326:Coronary Circulation; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin; D007213:Indomethacin