HYPOXIA-REOXYGENATION IMPAIRS NO-MEDIATED VASODILATION IN RAT LUNGS

Isolated rat lungs subjected to hypoxia-reoxygenation (WR) were used t o study NO-mediated pulmonary vasodilation during oxidant-induced vasc ular injury. After ventilation with 3% O-2, reoxygenation with 21% (H/ R 21%) or 95% O-2 (H/R 95%) caused lung edema and lipid peroxidation. Vasodilation to A23187 was attenuated after H/R 21% and abolished afte r H/R 95%. The vasodilator-response curve to NO was more shifted to th e right after H/R 95% than after H/R 21%. Pretreatment with superoxide dismutase (SOD; 150 U/ml) and catalase (120 U/ml) prevented impairmen t of A23187- and NO-mediated vasodilation. SOD and catalase added afte r reoxygenation restored vasodilation to NO but not to A23187. In lung s obtained from chronically hypoxic rats but studied under conditions of normoxic ventilation, vasodilation to A23187 was abolished, but vas odilation to NO remained unchanged. The data suggest that generation o f oxygen-derived reactive species after WR produces impairment of NO f ormation as well as direct inactivation of NO. This does not explain t he decreased endothelial NO-mediated pulmonary vasodilation in chronic ally hypoxic rats.