Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A 2 biosynthesis in lung, spleen or platelets

Abstract

Infusion of arachidonic acid through the guinea pig lung or the cat spleen causes a release of thromboxane A 2 and prostaglandins, as measured by bioassay. After incubation of human platelets with arachidonate similar metabolites are formed, as demonstrated chromatographically. Infusion of imidazole (50–75 μg/ml) through the lung or spleen specifically inhibits thromboxane A 2 production and diverts the pathway to the prostaglandins, mainly prostaglandin F 2α. In human platelets imidazole causes a dose-dependent inhibition of thromboxane A 2 formation (ID 50 5.5 × 10 −4 M). This inhibition is accompanied by a dose-dependent increase in prostaglandin F 2α. Since thromboxane A 2 induces platelet aggregation and is a potent vasoconstrictor, diversion of pathways to prostaglandins with opposite or less potent actions might be of relevance in the treatment of cardiovascular diseases.