• Matthias Lange, Yoshimitsu Nakano, Daniel L Traber, Atsumori Hamahata, Aimalohi Esechie, Collette Jonkam, Kamna Bansal, Lillian D Traber, and Perenlei Enkhbaatar.
• Department of Anesthesiology, Investigational Intensive Care Unit, The University of Texas Medical Branch and Shriners Hospitals for Children, Galveston, TX 77550, USA. lanm@gmx.de
• Biochem. Biophys. Res. Commun. 2010 Aug 20; 399 (2): 286-91.

AbstractExcessive production of nitric oxide (NO) by NO synthase (NOS) with subsequent formation of peroxynitrite and poly(adenosine diphosphate ribose) is critically implemented in the pathophysiology of acute lung injury and sepsis. To elucidate the roles of different isoforms of NOS, we tested the effects of non-selective NOS inhibition and neuronal NOS (nNOS)- and inducible NOS (iNOS)-gene deficiency on the pulmonary oxidative and nitrosative stress reaction in a murine sepsis model. The injury was induced by four sets of cotton smoke using an inhalation chamber and subsequent intranasal administration of live Pseudomonas aeruginosa (3.2x10(7) colony-forming units). In wild type mice, the injury was associated with excessive releases of pro-inflammatory cytokines in the plasma, enhanced neutrophil accumulation, increased lipid peroxidation, and excessive formation of reactive nitrogen species and vascular endothelial growth factor in the lung. Both nNOS- and iNOS-gene deficiency led to significantly reduced oxidative and nitrosative stress markers in the lung, but failed to significantly improve survival. Treatment with a non-selective NOS inhibitor failed to reduce the oxidative and nitrosative stress reaction to the same extent and even tended to increase mortality. In conclusion, the current study demonstrates that both nNOS and iNOS are partially responsible for the pulmonary oxidative and nitrosative stress reaction in this model. Future studies should investigate the effects of specific pharmacological inhibition of nNOS and iNOS at different time points during the disease process.Copyright 2010 Elsevier Inc. All rights reserved.

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