Role of different nitric oxide synthase isoforms in a murine model of acute lung injury and sepsis

Biochemical and Biophysical Research Communications
Matthias LangePerenlei Enkhbaatar

Abstract

Excessive 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 a...Continue Reading

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Citations

Mar 16, 2011·Clinical and Experimental Pharmacology & Physiology·Jin-Fu XuHui-Ping Li
Mar 8, 2012·Experimental Lung Research·Matthias LangePerenlei Enkhbaatar
Dec 28, 2010·Biochemical and Biophysical Research Communications·Matthias LangePerenlei Enkhbaatar
Sep 2, 2015·The Journal of Experimental Medicine·Mirza Saqib BaigMarcelo G Bonini
Apr 24, 2015·Medical Microbiology and Immunology·Luiz Gonzaga da CunhaAlessandra Mattos Saliba
Aug 2, 2011·Respiratory Physiology & Neurobiology·Raquel S SantosPatricia R M Rocco
Oct 9, 2014·The Journal of Surgical Research·Madhu C LingarajuSurendra K Tandan
May 9, 2018·Inflammation·Yong ChenZhidong Zhou
Sep 13, 2019·Intensive Care Medicine Experimental·Osamu FujiwaraPerenlei Enkhbaatar
Apr 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mansi Srivastava, Mirza S Baig

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