title: Oxygen tension and inhaled nitric oxide modulate pulmonary levels of S-nitrosocysteine and 3-nitrotyrosine in rats.
abstract: The oxidative environment within the lung generated upon administration of oxygen may be a critical regulator for the efficacy of inhaled nitric oxide therapy, possibly as a consequence of changes in nitrosative and nitrative chemistry. Changes in S-nitrosocysteine and 3-nitrotyrosine adducts were therefore evaluated after exposure of rats to 80% or >95% oxygen for 24 or 48 h with and without 20 ppm inhaled nitric oxide. Exposure to 80% oxygen led to increased formation of S-nitrosocysteine and 3-nitrotyrosine adducts in lung tissue that were also associated with increased expression of iNOS. The addition of inhaled nitric oxide in 80% oxygen exposure did not alter any of these adducts in the lung or in the bronchoalveolar lavage (BAL). Exposure to >95% oxygen led to a significant decrease in S-nitrosocysteine and an increase in 3-nitrotyrosine adducts in the lung. Co-administration of inhaled nitric oxide with >95% oxygen prevented the decrease in S-nitrosocysteine levels. The levels of S-nitrosocysteine and 3-nitrotyrosine returned to baseline in a time-dependent fashion after termination of exposure to >95% oxygen and inhaled nitric oxide. These data suggest the formation of S-nitrosating and tyrosine-nitrating species is regulated by oxygen tensions and co-administration of inhaled nitric oxide restores the nitrosative chemistry without a significant impact upon the nitrative pathway.
authors.affiliation: The Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lorch
authors.forename: David
authors.initials: D
authors.lastname: Munson
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lightfoot
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D026403:S-Nitrosothiols / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C021315:S-nitrosocysteine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003545:Cysteine; D010100:Oxygen