Hypoxia-reoxygenation impairs NO-mediated vasodilation in rat lungs

Isolated rat lungs subjected to hypoxia-reoxygenation (H/R) were used to study NO-mediated pulmonary vasodilation during oxidant-induced vascular injury. After ventilation with 3% O2, reoxygenation with 21% (H/R 21%) or 95% O2 (H/R 95%) caused lung edema and lipid peroxidation. Vasodilation to A23187 was attenuated after H/R 21% and abolished after H/R 95%. The vasodilator-response curve to NO was more shifted to the right after H/R 95% than after H/R 21%. Pretreatment with superoxide dismutase (SOD; 150 U/ml) and catalase (120 U/ml) prevented impairment of A23187- and NO-mediated vasodilation. SOD and catalase added after reoxygenation restored vasodilation to NO but not to A23187. In lungs obtained from chronically hypoxic rats but studied under conditions of normoxic ventilation, vasodilation to A23187 was abolished, but vasodilation to NO remained unchanged. The data suggest that generation of oxygen-derived reactive species after H/R produces impairment of NO formation as well as direct inactivation of NO. This does not explain the decreased endothelial NO-mediated pulmonary vasodilation in chronically hypoxic rats.