Effects of peroxynitrite on pulmonary edema and the oxidative state

Excess nitric oxide (NO) generation in the presence of superoxide anion (O2-) leads to the formation of peroxynitrite which may result in lung injury. Oxidant-mediated lung injury has a critical role in pulmonary diseases. We therefore determined whether peroxynitrite causes lung fluid accumulation, lipid peroxidation, and formation of nitrotyrosine using an isolated perfused rat lung model. The lung weight gain during bolus peroxynitrite infusion increased in a dose-dependent manner over a range of 3 to 30 mumole. Concomitantly, bronchoalveolar lavage Ficoll also increased, indicative of increased endothelial permeability. Peroxynitrite increased the production of thiobarbituric acid reactive substances, an index of lipid peroxidation. Furthermore, nitrotyrosine levels in lung tissue rose with increased concentration of peroxynitrite, as determined by Western blot using antinitrotyrosine antibodies. These results suggest that peroxynitrite, formed from NO and O2-, leads to increased pulmonary fluid accumulation, possibly through lipid peroxidation and/or nitration of cell membrane proteins.