Recent evidence suggests that the platelet-inhibitory drugs sulfin-pyrazone and ibuprofen may have value in treatment of coronary artery disease. However, these drugs do not only block platelet aggregation, but also block synthesis by blood vessels of prostaglandins that promote vasodilation. Platelets may differ from blood vessels in their sensitivity to sulfinpyrazone or ibuprofen. In theory, optimal doses for coronary disease would inhibit potentially deleterious platelet aggregation but not interfere with synthesis of possibly beneficial vasodilator prostaglandins. To determine whether it was possible to identify such optimal doses we measured the effects of intravenous sulfinpyrazone, 0.3-100 mg/kg (n = 9), or sodium ibuprofen, 0.1-3 mg/kg (n = 7), on vasodilation induced by the protaglandin precursor arachidonic acid. We also assessed drug effects on in vitro platelet aggregation in the same animals. Both sulfinpyrazone and ibuprofen caused a dose-related reduction in flow increment after arachidonic acid. Sulfinpyrazone, ≥10 mg/kg, and ibuprofen, ≥1 mg/kg, produced a mean reduction of least 60% (p < 0.02 for each) in the vasodilator response to 1 mg arachidonic acid. Sulfinpyrazone, 0.3 mg/kg, and ibuprofen, 0.1 mg/kg, had no consistent effects on flow. Flow rise after intracoronary prostaglandin E2 was undiminished by sulfinpyrazone or ibuprofen. Sulfinpyrazone, ≥10 mg/kg, and ibuprofen, ≥1 mg/kg, markedly inhibited platelet aggregation induced by adenosine diphosphate, 2.3 × 10-5 M (p < 0.01 for each). Sulfinpyrazone, 0.3 mg/kg, and ibuprofen, 0.1 mg/kg, failed to alter platelet aggregation. Hence, sulfinpyrazone and ibuprofen doses inhibiting platelet function also produced comparable inhibition of arachidonic acid-induced coronary vasodilation, presumably by interfering with arachidonic acid conversion to vasodilator prostaglandins. Neither sulfinpyrazone nor ibuprofen, administered acutely, appears to have an “optimal“ dose that in hibits in vitro platelet aggregation without producing inhibition of the synthesis of vasodilator prostaglandins.
- Coronary vasodilation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine