Human platelets modulate edema formation in isolated rabbit lungs.
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.
Heffner
J E
JE
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Cook
J A
JA
Halushka
P V
PV
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011654:Pulmonary Edema / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D011817:Rabbits; D013929:Thromboxane B2 / Q000378:metabolism; D014969:Xanthine Oxidase / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011687:Purines; D003687:Dehydroepiandrosterone; D013929:Thromboxane B2; C045749:SQ 29548; D010208:Papaverine; D005954:Glucosephosphate Dehydrogenase; D014969:Xanthine Oxidase; D001241:Aspirin; C030985:purine