title: Nitrotyrosine and NO synthases in infants with respiratory failure: influence of inhaled NO.
abstract: Inhaled nitric oxide (NO) is a selective vasodilator in pulmonary hypertension. However, the safety of inhaled NO (iNO) has not been established. Using an immunohistochemical technique, we studied the expression of NO synthase (NOS) isoforms NOS1, NOS2, NOS3, and nitrotyrosine, the marker of toxic NO-superoxide pathway, in lung specimens from autopsies. Twelve infants dying with respiratory failure had iNO up to 60 parts per million for 0.1-15 days. Twelve control infants were matched in pairs on the basis of the diagnosis, number of gestational days at birth, age at death, and whether extracorporeal perfusion was required. In addition, 5 infants who died of SIDS or nonpulmonary trauma (healthy lungs) were compared to 8 age-matched cases with respiratory failure. Immunostaining was graded by the intensity of the color deposit and the frequency in specific cells stained. Inhaled NO tended to increase NOS2 expression in bronchiolar epithelium and adjacent tissue. There were no other differences in the distribution of nitrotyrosine or NOS isoforms between iNO-treated infants and the control group with respiratory failure. All NOS isoforms were evident in the lungs studied. In severe respiratory failure, nitrotyrosine was mostly detectable in the bronchiolar epithelium and alveolar exudates, whereas in healthy lungs those sites did not contain nitrotyrosine. The alveolar tissue of infants with progressive respiratory may be affected by the NO-superoxide pathway. However, inhalation of NO was not associated with a detectable increase in oxidant stress.
authors.affiliation: Department of Pediatrics, University of Oulu, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Aikio
authors.forename: Katri
authors.initials: K
authors.lastname: Vuopala
authors.forename: Marja-Leena
authors.initials: ML
authors.lastname: Pokela
authors.forename: Sture
authors.initials: S
authors.lastname: Andersson
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
mesh_terms: D000280:Administration, Inhalation; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000009:adverse effects; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000187:drug effects; D009603:Nitroso Compounds / Q000032:analysis*; D012044:Regression Analysis; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000201:enzymology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C443112:3-nitrosotyrosine; D009603:Nitroso Compounds; D014665:Vasodilator Agents; D009569:Nitric Oxide; D014443:Tyrosine; D019001:Nitric Oxide Synthase