| First Author | Peng X | Year | 2005 |
| Journal | Am J Respir Crit Care Med | Volume | 172 |
| Issue | 4 | Pages | 470-9 |
| PubMed ID | 15937288 | Mgi Jnum | J:114335 |
| Mgi Id | MGI:3688792 | Doi | 10.1164/rccm.200411-1547OC |
| Citation | Peng X, et al. (2005) Inducible nitric oxide synthase contributes to ventilator-induced lung injury. Am J Respir Crit Care Med 172(4):470-9 |
| abstractText | 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. |
