Nitric oxide synthase 3 contributes to ventilator-induced lung injury
Vaporidi K, Francis RCE, Bloch KD, Zapol WM (2010)
Publication Type: Journal article, Review article
Publication year: 2010
Journal
American Journal of Physiology-Lung Cellular and Molecular Physiology
American Physiological Society
Book Volume: 299
Pages Range: L150-L159
Journal Issue: 2
DOI: 10.1152/ajplung.00341.2009
Abstract
Nitric oxide synthase (NOS) depletion or inhibition reduces ventilator-induced lung injury (VILI), but the responsible mechanisms remain incompletely defined. The aim of this study was to elucidate the role of endothelial NOS, NOS3, in the pathogenesis of VILI in an in vivo mouse model. Wild-type and NOS3-deficient mice were ventilated with high-tidal volume (HVT; 40 ml/kg) for 4 h, with and without adding NO to the inhaled gas. Additional wild-type mice were pretreated with tetrahydrobiopterin and ascorbic acid, agents that can prevent NOS-generated superoxide production. Arterial blood gas tensions, histology, and lung mechanics were evaluated after 4 h of HVT ventilation. The concentration of protein, IgM, cytokines, malondialdehyde, and 8-isoprostane were measured in bronchoalveolar lavage fluid (BALF). Myeloperoxidase activity, total and oxidized glutathione levels, and NOS-derived superoxide production were measured in lung tissue homogenates. HVT ventilation induced VILI in wild-type mice, as reflected by decreased lung compliance, increased concentrations of protein and cytokines in BALF, and oxidative stress. All indices of VILI were ameliorated in NOS3-deficient mice. Augmenting pulmonary NO levels by breathing NO during mechanical ventilation did not increase lung injury in NOS3-deficient mice. HVT ventilation increased NOS-inhibitable superoxide production in lung extracts from wild-type mice but not in those from NOS3-deficient mice. Administration of tetrahydrobiopterin and ascorbic acid ameliorated VILI in wild-type mice. Our results indicate that NOS3 contributes to ventilator-induced lung injury via increased production of superoxide. Copyright © 2010 the American Physiological Society.
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APA:
Vaporidi, K., Francis, R.C.E., Bloch, K.D., & Zapol, W.M. (2010). Nitric oxide synthase 3 contributes to ventilator-induced lung injury. American Journal of Physiology-Lung Cellular and Molecular Physiology, 299(2), L150-L159. https://dx.doi.org/10.1152/ajplung.00341.2009
MLA:
Vaporidi, Katerina, et al. "Nitric oxide synthase 3 contributes to ventilator-induced lung injury." American Journal of Physiology-Lung Cellular and Molecular Physiology 299.2 (2010): L150-L159.
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