HYDROGEN PEROXIDE-INDUCED BRONCHO-INDUCED AND VASOCONSTRICTION IN THE ISOLATED-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 ventilated guinea pig lungs was investigated. Hydrogen peroxide (50 muM in the perfusion buffer) induced a decrease in G(aw) and C(dyn) and perfusion flow during 5 min. of exposure. Hydrogen peroxide also caused an increase in the levels of thromboxane in the perfusate of the lung. The constrictor effects as well as the formation of thromboxane were inhibited by the cyclooxygenase inhibitor ibuprofen (50 muM). The thromboxane/prostaglandin endoperoxide receptor antagonist L-670,596 (1 muM) abolished the effects of hydrogen peroxide on perfusion flow, G(aw) and C(dyn), but did not affect the formation of thromboxane. The thromboxane-synthetase inhibitor carboxyheptylimidazole (100 muM) reduced both 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-activating factor in mediating the effect of hydrogen peroxide could not be supported, as the platelet-activating factor receptor antagonist WEB 2086 (10 muM) did not affect hydrogen peroxide induced vaso- and bronchoconstriction. The results of this study show that hydrogen peroxide induces thromboxane A2 mediated vaso- and bronchoconstriction in the isolated perfused and ventilated guinea pig lung. Platelet-activating factor does not appear to play a significant role in the hydrogen peroxide-induced vaso- and bronchoconstriction. Our results also suggest that the perfused guinea pig lung is more sensitive to hydrogen peroxide than the perfused rat lung.