HYDROGEN PEROXIDE-INDUCED BRONCHO-INDUCED AND VASOCONSTRICTION IN THEISOLATED-PERFUSED AND VENTILATED GUINEA-PIG LUNG

The effect of hydrogen peroxide on perfusion flow, airway conductance (G(aw)) and dynamic compliance (C(dyn)) of isolated perfused and venti lated guinea pig lungs was investigated. Hydrogen peroxide (50 muM in the perfusion buffer) induced a decrease in G(aw) and C(dyn) and perfu sion flow during 5 min. of exposure. Hydrogen peroxide also caused an increase in the levels of thromboxane in the perfusate of the lung. Th e constrictor effects as well as the formation of thromboxane were inh ibited by the cyclooxygenase inhibitor ibuprofen (50 muM). The thrombo xane/prostaglandin endoperoxide receptor antagonist L-670,596 (1 muM) abolished the effects of hydrogen peroxide on perfusion flow, G(aw) an d C(dyn), but did not affect the formation of thromboxane. The thrombo xane-synthetase inhibitor carboxyheptylimidazole (100 muM) reduced bot h the hydrogen peroxide-induced formation of thromboxane and vaso- and bronchoconstriction, suggesting a predominant role for thromboxane A2 versus prostaglandin H-2 in these effects. A role for platelet-activa ting factor in mediating the effect of hydrogen peroxide could not be supported, as the platelet-activating factor receptor antagonist WEB 2 086 (10 muM) did not affect hydrogen peroxide induced vaso- and bronch oconstriction. The results of this study show that hydrogen peroxide i nduces thromboxane A2 mediated vaso- and bronchoconstriction in the is olated perfused and ventilated guinea pig lung. Platelet-activating fa ctor does not appear to play a significant role in the hydrogen peroxi de-induced vaso- and bronchoconstriction. Our results also suggest tha t the perfused guinea pig lung is more sensitive to hydrogen peroxide than the perfused rat lung.