Nitration of proteins in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome receiving inhaled nitric oxide

Inhaled nitric oxide (NO) is used to improve gas exchange and reduce pulmonary vascular resistance (PVR) in patients with the acute respiratory distress syndrome (ARDS). Although controlled studies have shown no survival benefit, some investigators have suggested that inhaled NO may have antiinflammatory properties under these circumstances. In contrast, others have speculated that NO given by inhalation could be cytotoxic, as it combines with superoxide at near diffusion-limited rates to produce the highly reactive oxidant peroxynitrite (ONOO-). We therefore quantified levels of 3-nitrotyrosine, a marker for ONOO- formation, in bronchoalveolar lavage fluid (BAL) from patients with ARDS receiving inhaled NO, and from patients with comparable lung injury who were not so treated. We also measured levels of 3-chlorotyrosine as an index of neutrophil activation to assess indirectly the effects of inhaled NO on lung inflammation. Patients receiving NO had increased levels of 3-nitrotyrosine (6.76 +/- 2.79 versus 0.4 +/- 0.15 nmol/mg of protein, p < 0.05) and 3-chlorotyrosine (7.97 +/- 2.74 versus 1.53 +/- 1.09 nmol/mg of protein, p < 0.05) in BAL protein compared with controls. In patients with ARDS, inhaled NO increases the formation of 3-nitrotyrosine and is accompanied by an increase in levels of 3-chlorotyrosine (a marker of neutrophil activation). The possible long-term consequences of these observations remain to be evaluated.