Role of pulmonary artery reactivity and nitric oxide in injury and inflammation following lung contusion

Satyanarayana Lakshminrusimha, Madathilparambil V. Suresh, Paul R. Knight, Sylvia F. Gugino, Bruce A. Davidson, Jadwiga D. Helinski, Lori C. Nielsen, James A. Russell, Bi Yu, Lixia Zeng, Subramaniam Pennathur, Krishnan Raghavendran

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The mechanisms contributing to hypoxia in lung contusion (LC) remain unclear and not temporally associated with the peak onset of acute inflammation. We investigated the role of oxidative stress in alteration of pulmonary arterial (PA) reactivity following LC. In addition, the role of antioxidants in reversing this process was examined. PaO2 and PA reactivity were measured in rats subjected to bilateral LC. Rings were pretreated with a nitric oxide synthase (NOS) inhibitor, L-nitro arginine (10 M), or PEG-superoxide dismutase (SOD) and PEG-catalase (CAT), or both (L-nitro arginine + SOD/CAT). Rings were constricted with norepinephrine and relaxed with an NOS agonist (A23187) or NO donor (SNAP [S-nitrosyl amino penicillamine]). Immunochemical and mass spectrometric quantification for nitrotyrosine was performed. Rats were hypoxemic at 4 h after contusion compared with controls, but recovered by 24 h (PaO2/FIO2 ratio: baseline, 443 ± 28; 4 h, 288 ± 46; and 24 h, 417 ± 23). Pulmonary arterial constriction to NOS inhibition and relaxation to A23187 were impaired 4 h after LC. Pulmonary arterial relaxation to SNAP was decreased at 4 and 24 h after LC. These alterations in PA reactivity were reversed by SOD/CAT pretreatment. SOD1 and 2 mRNA were upregulated, and soluble guanylyl cyclase mRNA was downregulated 24 h after LC. Immunohistochemistry and mass spectrometry revealed that levels of 3-nitrotyrosine were increased markedly at 4 h following LC consistent with superoxide generation and formation of peroxynitrite. Collectively, these data suggest that consumption of NO due to excess superoxide resulting in peroxynitrite formation leads to diminished vascular reactivity following LC.

Original languageEnglish (US)
Pages (from-to)278-285
Number of pages8
JournalShock
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Keywords

  • Hypoxemia
  • inflammation
  • lung contusion
  • nitric oxide
  • reactive oxygen and nitrogen species

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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    Lakshminrusimha, S., Suresh, M. V., Knight, P. R., Gugino, S. F., Davidson, B. A., Helinski, J. D., Nielsen, L. C., Russell, J. A., Yu, B., Zeng, L., Pennathur, S., & Raghavendran, K. (2013). Role of pulmonary artery reactivity and nitric oxide in injury and inflammation following lung contusion. Shock, 39(3), 278-285. https://doi.org/10.1097/SHK.0b013e318281d6ed