Inducible nitric oxide synthase contributes to ventilator-induced lung injury

Xinqi Peng, Raja Elie E. Abdulnour, Saad Sammani, Shwu Fan Ma, Eugenia J. Han, Emile J. Hasan, Rubin Tuder, Joe G.N. Garcia, Paul M. Hassoun

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Rationale: Inducible nitric oxide synthase (iNOS) has been implicated in the development of acute lung injury. Recent studies indicate a role for mechanical stress in iNOS and endothelial NOS (eNOS) regulation. Objectives: This study investigated changes in lung NOS expression and activity in a mouse model of ventilator-induced lung injury. Methods: C57BL/6J (wild-type [WT]) and iNOS-deficient (iNOS-/-) mice received spontaneous ventilation (control) or mechanical ventilation (MV; VT of 7 and 20 ml/kg) for 2 hours, after which NOS gene expression and activity were determined and pulmonary capillary leakage assessed by the Evans blue albumin assay. Results: iNOS mRNA and protein expression was absent in iNOS-/- mice, minimal in WT control mice, but significantly upregulated in response to 2 hours of MV. In contrast, eNOS protein was decreased in WT mice, and nonsignificantly increased in iNOS-/- mice, as compared with control animals. iNOS and eNOS activities followed similar patterns in WT and iNOS-/- mice, MV caused acute lung injury as suggested by cell infiltration and nitrotyrosine accumulation in the lung, and a significant increase in bronchoalveolar lavage cell count in WT mice, findings that were reduced in iNOS-/- mice. Finally, Evans blue albumin accumulation in lungs of WT mice was significant (50 vs. 15% increase in iNOS-/- mice compared with control animals) in response to MV and was prevented by treatment of the animals with the iNOS inhibitor aminoguanidine. Conclusion: Taken together, our results indicate that iNOS gene expression and activity are significantly upregulated and contribute to lung edema in ventilator-induced lung injury.

Original languageEnglish (US)
Pages (from-to)470-479
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume172
Issue number4
DOIs
StatePublished - Aug 15 2005
Externally publishedYes

Keywords

  • Inducible nitric oxide synthase
  • Lung permeability
  • Mechanical ventilation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Peng, X., Abdulnour, R. E. E., Sammani, S., Ma, S. F., Han, E. J., Hasan, E. J., Tuder, R., Garcia, J. G. N., & Hassoun, P. M. (2005). Inducible nitric oxide synthase contributes to ventilator-induced lung injury. American journal of respiratory and critical care medicine, 172(4), 470-479. https://doi.org/10.1164/rccm.200411-1547OC