Immunohistochemical localization of protein 3-nitrotyrosine and S-nitrosocysteine in a murine model of inhaled nitric oxide therapy

Inhaled nitric oxide (INO) therapy is currently used clinically to selectiv ely dilate the pulmonary vasculature and to help treat persistent pulmonary hypertension and bronchopulmonary dysplasia in the neonate. However, in th e presence of oxygen or superoxide, nitric oxide forms potentially harmful reactive nitrogen species. Using an experimental mice model, we examined th e effects of concurrent hyperoxia and INO on protein tyrosine nitration and cysteine S-nitrosylation in pulmonary tissue. Data showed enhanced S-nitro tyrosine staining within the airway epithelium and alveolar interstitium of mice lungs treated with hyperoxia, which did not increase significantly wi th INO administration. Within the alveolar interstitium, 3-nitrotyrosine st aining was localized to macrophages. S-Nitrosocysteine staining in airway e pithelium was significantly enhanced with INO administration regardless of oxygen content. These data suggest that the formation of protein S-nitrosoc ysteine is the major protein modification during administration of INO.