Relative effects of aspirin on platelet aggregation and prostaglandin-mediated coronary vasodilatation in the dog.
Aspirin, as an inhibitor of platelet aggregation, may be of benefit in ischemic heart disease. However, aspirin blocks not only platelet aggregation but also synthesis of prostacyclin, a vasodilator and platelet deaggregator. The relative sensitivity of prostaglandin-mediated coronary vasodilatation and platelet aggregation to inhibition by aspirin remains uncertain. We therefore investigated the relative dose-response relationship of aspirin on arachidonic acid-induced increments in coronary blood flow and on ADP-induced aggregation of platelets. In 11 open-chest dogs, intracoronary arachidonic acid, 0.1-3.0 mg, produced dose-related increases in coronary blood flow that were inhibited progressively by i.v. aspirin over the dose range 0.3-3.0 mg/kg. Aspirin at 3 mg/kg almost completely obliterated the response to 3 mg of arachidonic acid. Similarly, aspirin doses of 0.3-3.0 mg/kg progressively raised the minimal concentration of ADP necessary for platelet aggregation. The threshold concentration of ADP that produced aggregation of platelets from 10 control dogs ranged from 2.3 x 10(-6) M to 1.2 x 10(-5) M. Aspirin at 3 mg/kg completely inhibited aggregation of platelets from 11 of 12 dogs, even with ADP at 2.3 x 10(-4) M concentration, the maximum tested. Aspirin at 0.1 mg/kg failed to inhibit either ADP-induced platelet aggregation or arachidonic acid-induced increments in coronary blood flow. Thus, the two test systems showed similar sensitivity to inhibition by aspirin with respect to threshold dose and maximal effect. These results show that very low doses of aspirin inhibit arachidonic acid-induced coronary vasodilatation and that aspirin at low doses does not appear to selectively inhibit platelet activity relative to coronary vasodilatation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D001095:Arachidonic Acids; D011453:Prostaglandins; D000244:Adenosine Diphosphate; D001241:Aspirin