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

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

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Ventilator-Induced Lung Injury
Nitric Oxide Synthase Type II
Lung
Evans Blue
Acute Lung Injury
Albumins
Gene Expression
Mechanical Stress
Bronchoalveolar Lavage
Artificial Respiration

Keywords

  • Inducible nitric oxide synthase
  • Lung permeability
  • Mechanical ventilation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Inducible nitric oxide synthase contributes to ventilator-induced lung injury. / Peng, Xinqi; Abdulnour, Raja Elie E; Sammani, Saad; Ma, Shwu Fan; Han, Eugenia J.; Hasan, Emile J.; Tuder, Rubin; Garcia, Joe G N; Hassoun, Paul M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 4, 15.08.2005, p. 470-479.

Research output: Contribution to journalArticle

Peng, X, Abdulnour, REE, Sammani, S, Ma, SF, Han, EJ, Hasan, EJ, Tuder, R, Garcia, JGN & Hassoun, PM 2005, 'Inducible nitric oxide synthase contributes to ventilator-induced lung injury', American Journal of Respiratory and Critical Care Medicine, vol. 172, no. 4, pp. 470-479. https://doi.org/10.1164/rccm.200411-1547OC
Peng, Xinqi ; Abdulnour, Raja Elie E ; Sammani, Saad ; Ma, Shwu Fan ; Han, Eugenia J. ; Hasan, Emile J. ; Tuder, Rubin ; Garcia, Joe G N ; Hassoun, Paul M. / Inducible nitric oxide synthase contributes to ventilator-induced lung injury. In: American Journal of Respiratory and Critical Care Medicine. 2005 ; Vol. 172, No. 4. pp. 470-479.
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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.",
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T1 - Inducible nitric oxide synthase contributes to ventilator-induced lung injury

AU - Peng, Xinqi

AU - Abdulnour, Raja Elie E

AU - Sammani, Saad

AU - Ma, Shwu Fan

AU - Han, Eugenia J.

AU - Hasan, Emile J.

AU - Tuder, Rubin

AU - Garcia, Joe G N

AU - Hassoun, Paul M

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N2 - 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.

AB - 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.

KW - Inducible nitric oxide synthase

KW - Lung permeability

KW - Mechanical ventilation

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