The differential effects of aspirin on platelets, leucocytes and vascular endothelium in an in vivo model of thrombus formation.
Unanswered questions remain with regard to the therapeutic use of aspirin and the selective inhibition of thromboxane A2 and prostacyclin in platelets and endothelial cells. In the present study, the effects of aspirin on platelets and endothelial cells in vivo were examined using a helium-neon (He-Ne) laser-induced thrombosis model. Single intravenous injections of aspirin at concentrations of more than 0.5 mg/kg body weight mediated a dose dependent inhibition of thrombus formation in arterioles but not in venules. This antithrombotic effect was optimum after 15 min and declined after 90 min. Potent antithrombotic activity in arterioles was manifest at doses of 2.5 mg/kg to 50 mg/kg, and initial inhibition of thrombogenesis in vivo was most pronounced at high doses. Oral aspirin also inhibited thrombus formation in arterioles but not in venules, although the antithrombotic effects were delayed and prolonged. Maximum inhibition of ex vivo, collagen induced platelet aggregation by aspirin was observed approximately 180 min after intravenous injection. The results demonstrated that, although aspirin might have differential effects on platelets and endothelial cells, potent antithrombotic activity was manifest in arterioles at all concentrations. The findings suggest that the concept of the aspirin dilemma might be ignored for therapeutic purposes in many clinical circumstances. The antithrombotic effects of aspirin were unchanged in granulocyte-depleted animals, indicating that leucocyte-related mechanisms including neutrophil superoxide anion production did not modulate the potency of aspirin in this model.
Nagamatsu
Y
Y
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Japan.
Tsujioka
Y
Y
Hashimoto
M
M
Giddings
J C
JC
Yamamoto
J
J
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D007834:Lasers; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D051381:Rats; D013927:Thrombosis / Q000097:blood* / Q000209:etiology
D001241:Aspirin