sq-29548 and purine

The role of platelet glucose-6-phosphate dehydrogenase (G-6-PD) in mediating the effects of human platelets on oxidant-induced edema in the isolated perfused rabbit lung was investigated using dehydroepiandrosterone, a specific steroidal inhibitor of G-6-PD. Xanthine oxidase (0.003 and 0.012 U/ml) caused lung edema that was attenuated by coinfusion of washed human platelets. Platelets that were incubated with DEA to inhibit G-6-PD activity augmented xanthine oxidase-induced lung edema and pulmonary hypertension at both doses of xanthine oxidase. Infusion of papaverine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets. It was concluded that antioxidant-intact platelets attenuate oxidant-induced lung edema by preventing increased membrane permeability, and that G-6-PD-inhibited platelets augment lung edema through hydrostatic mechanisms mediated by release of platelet cyclooxygenase products.

Topics: Animals; Aspirin; Blood Platelets; Bridged Bicyclo Compounds, Heterocyclic; Dehydroepiandrosterone; Fatty Acids, Unsaturated; Female; Glucosephosphate Dehydrogenase; Humans; Hydrazines; Male; Papaverine; Perfusion; Pulmonary Edema; Pulmonary Wedge Pressure; Purines; Rabbits; Thromboxane B2; Xanthine Oxidase