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 (O2) or both, on free radical-mediated changes in macromolecules, i.e. lipids and proteins, in vivo. Wistar rats were exposed to > 95% O2 or 40 ppm NO, or both, for 6 h. Rats in 21% O2 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).


CONCLUSIONS
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.
Turanlahti
M
M
Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland.
Pesonen
E
E
Lassus
P
P
Andersson
S
S
D000818:Animals; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D018496:Hyperoxia / Q000378:metabolism*; D015227:Lipid Peroxidation; D008168:Lung / Q000201:enzymology; D008171:Lung Diseases / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000627:therapeutic use*; D018384:Oxidative Stress; D010100:Oxygen / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D009569:Nitric Oxide; D010100:Oxygen