Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model

R. Sugimoto, T. Okamoto, A. Nakao, J. Zhan, Y. Wang, J. Kohmoto, D. Tokita, C. F. Farver, M. M. Tarpey, T. R. Billiar, M. T. Gladwin, K. R. McCurry

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28 Citations (Scopus)

Abstract

Ischemia/reperfusion injury (IRI) is the most common cause of early mortality following lung transplantation (LTx). We hypothesized that nitrite, an endogenous source of nitric oxide (NO), may protect lung grafts from IRI. Rat lung grafts were stored in preservation solution at 4°C for 6 hours. Both grafts and recipients were treated with nitrite. Nitrite treatment was associated with significantly higher levels of tissue oxygenation, lower levels of cytokines and neutrophil/macrophage infiltration, lower myeloperoxidase activity, reduced oxidative injury and increased cGMP levels in grafts than in the controls. Treatment with either a nitric oxide scavenger or a soluble guanylyl cyclase (sGC) inhibitor diminished the beneficial effects of nitrite and decreased cGMP concentrations. These results suggest that nitric oxide, generated from nitrite, is the molecule responsible for the effects of nitrite via the nitric oxide/sGC/cGMP pathway. Allopurinol, a xanthine oxidoreductase (XOR) inhibitor, abrogated the protective effects of nitrite, suggesting that XOR is a key enzyme in the conversion of nitrite to nitric oxide. In vitro experiments demonstrated that nitrite prevented apoptosis in pulmonary endothelial cells. Nitrite also exhibits longer survival rate in recipients than control. In conclusion, nitrite inhibits lung IRI following cold preservation and had higher survival rate in LTx model.

Original languageEnglish
Pages (from-to)2938-2948
Number of pages11
JournalAmerican Journal of Transplantation
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Nitrite
  • ischemia reperfusion injury
  • lung transplantation
  • nitric oxide
  • rat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Sugimoto, R., Okamoto, T., Nakao, A., Zhan, J., Wang, Y., Kohmoto, J., Tokita, D., Farver, C. F., Tarpey, M. M., Billiar, T. R., Gladwin, M. T., & McCurry, K. R. (2012). Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model. American Journal of Transplantation, 12(11), 2938-2948. https://doi.org/10.1111/j.1600-6143.2012.04169.x