Effects of antiaggregant and antiinflammatory doses of aspirin on coronaryhemodynamics and myocardial reactive hyperemia in conscious dogs

Clinical studies have shown that low doses of aspirin (<300 mg/day) inhibit thromboxane A(2) production and platelet aggregation but preserve prostacy clin synthesis. In contrast, high doses of aspirin (>1,000 mg/day) suppress the syn, thesis of both eicosanoids. Because the consequences of aspirin a dministration have never been investigated on coronary vasomotor tone in vi vo, we investigated the effects of low and high doses of aspirin on systemi c and coronary hemodynamics under basal conditions and after myocardial rea ctive hyperemia in conscious dogs. Dogs were instrumented with a Doppler Ro w probe and a hydraulic occluder. Coronary blood flow was measured in the c onscious state at baseline and during myocardial reactive hyperemia after 1 0, 20, and 30 s of coronary occlusion. Thromboxane B-2 serum concentrations , an index of platelet aggregation, decreased by >90% after long-term i.v. administration of aspirin, 100 mg/day for 7 days (low dose). Neither system ic and coronary hemodynamics nor reactive hyperemia were affected by the dr ug. After combined administration of this low dose of aspirin and of the ni tric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine (L-NNA, 30 mg /kg/day/7 days), reactive hyperemia decreased to the same extent as when L- NNA was administered alone. After administration of a unique high-dose aspi rin (1,000 mg, i.v.), myocardial reactive hyperemia was markedly reduced, a nd this effect was still observed after previous blockade of NOS and cycloo xygenase by L-NNA and diclofenac, respectively. Thus long-term treatment wi th a low antiaggregant dose of aspirin does not alter the ability of corona ry vessels to dilate during myocardial reactive hyperemia in conscious dogs . In contrast, short-term administration of a high antiinflammatory dose of aspirin severely blunts myocardial reactive hyperemia through a mechanism that is independent of both cyclooxygenase and nitric oxide metabolic pathw ays.