Nitric oxide-related oxidants in acute lung injury

Nitric oxide (NO·) is a free radical and will react efficiently with other radicals. The reaction between NO· and superoxide anion (O₂^.-) is a pivotal reaction by which NO· affects oxidant metabolism. This reaction may scavenge O₂^.- before further reactions can occur that lead to the biosynthesis of more potent oxidants such as hydroxyl radical. The product of the reaction between NO· and O₂^.-, however, is peroxynitrite anion, which is also a potent oxidant capable of participating in several oxidative reactions. Among these reactions are oxidation of sulfhydryl groups, oxidation of lipids, and nitration of tyrosine by noncatalyzed and catalyzed mechanisms. The conformation, and therefore specific reactivity, of peroxynitrite are dependent on pH. Based on an understanding of this concept, sulfhydryl oxidation should be the predominant oxidative reaction of peroxynitrite in biological systems. Some experimental data support this conclusion. There is increasing evidence from isolated cell systems that peroxynitrite is produced under the influence of inflammatory mediators. Most data from animal models suggest that increased NO· production in acute lung injury is detrimental. We have performed immunohistochemical evaluation of lung tissue from pediatric patients with acute lung injury using an antinitrotyrosine antibody and have found evidence of extensive nitrotyrosine formation. This observation suggests a significant effect of peroxynitrite on lung tissue in this disorder. NO· has a variety of nonoxidant effects that also may have a role in acute lung injury. With the information currently available, one cannot conclude with certainty whether the net effect of increased NO· production in inflammatory disorders of the lung is beneficial or injurious. However, simultaneous increases in NO· and O₂^.- occurring during inflammation may lead to peroxynitrite formation and subsequent oxidative tissue injury.