Nitric oxide and hyperoxia in oxidative lung injury

Therapy with inhaled nitric oxide is usually given with high concentrations of oxygen. As nitric oxide (NO) is a free radical and hyperoxia increases oxygen radical production, we examined the effect of short exposure to NO or oxygen (O 2 ) or both, on free radical‐mediated changes in macromolecules, i.e. lipids and proteins, in vivo. Wistar rats were exposed to >95% O 2 or 40 ppm NO, or both, for 6 h. Rats in 21% O 2 served as controls. Lipid peroxidation was quantified as expired pentane, oxidative protein modification as carbonyl concentration, and pulmonary neutrophil accumulation as myeloperoxidase activity in the lungs. Hyperoxia for 6 h caused higher expired pentane (4.83 ± 1.39 pmol/min/100 g) and protein carbonylation (15.91 ± 2.49 nmol/mg) compared to controls (2.26 ± 1.00 pmol/min/100 g, and 7.40 ± 1.12 nmol/mg, respectively; both p < 0.05). After exposure to NO in air, protein carbonylation (14.50 ± 5.44 nmol/mg) and myeloperoxidase activity (4.85 ± 1.52 mU/mg) were higher than in controls (myeloperoxidase 2.49 ± 0.56 mU/mg; both p < 0.05). NO with hyperoxia decreased pentane (2.56 ± 1.51 pmol/min/ 100 g) and protein carbonylation (11.38 ± 3.58 nmol/mg) compared to hyperoxia (both p < 0.05). Conclusion : In vivo , 6 h exposure to hyperoxia or to 40 ppm NO induces free radical‐mediated lung injury. The combination of hyperoxia and 40 ppm NO significantly attenuates free radical‐mediated effects in the lungs compared to hyperoxia or 40 ppm NO in air.