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.
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Abbreviations
- 3NT:
-
3-nitrotyrosine
- BAL:
-
bronchoalveolar lavage
- CLD:
-
chronic lung disease
- ECMO:
-
extracorporeal membrane oxygenation
- NO:
-
nitric oxide
- eNOS:
-
endothelial nitric oxide synthase
- iNOS:
-
inducible nitric oxide synthase
- nNOS:
-
neuronal nitric oxide synthase
- PPHN:
-
persistent pulmonary hypertension
- SNO:
-
S-nitrosothiol
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Supported by National Institutes of Health, National Heart, Lung, and Blood Institute grant number HL-54926 and a Forrest Pharmaceutical Advancing Neonatal Care Grant.
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Lorch, S., Munson, D., Lightfoot, R. et al. Oxygen Tension and Inhaled Nitric Oxide Modulate Pulmonary Levels of S-Nitrosocysteine and 3-Nitrotyrosine in Rats. Pediatr Res 56, 345–352 (2004). https://doi.org/10.1203/01.PDR.0000134256.30519.9B
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DOI: https://doi.org/10.1203/01.PDR.0000134256.30519.9B
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