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

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

Research output: Contribution to journalArticle

25 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
Externally publishedYes

Fingerprint

Lung Transplantation
Acute Lung Injury
Nitrites
Nitric Oxide
Reperfusion Injury
Xanthine Dehydrogenase
Transplants
Lung
Survival Rate
Allopurinol
Neutrophil Infiltration
Peroxidase
Endothelial Cells
Macrophages
Apoptosis
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model. / Sugimoto, R.; Okamoto, T.; Nakao, Atsunori; Zhan, J.; Wang, Y.; Kohmoto, J.; Tokita, D.; Farver, C. F.; Tarpey, M. M.; Billiar, T. R.; Gladwin, M. T.; McCurry, K. R.

In: American Journal of Transplantation, Vol. 12, No. 11, 11.2012, p. 2938-2948.

Research output: Contribution to journalArticle

Sugimoto, R, Okamoto, T, Nakao, A, Zhan, J, Wang, Y, Kohmoto, J, Tokita, D, Farver, CF, Tarpey, MM, Billiar, TR, Gladwin, MT & McCurry, KR 2012, 'Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model', American Journal of Transplantation, vol. 12, no. 11, pp. 2938-2948. https://doi.org/10.1111/j.1600-6143.2012.04169.x
Sugimoto, R. ; Okamoto, T. ; Nakao, Atsunori ; Zhan, J. ; Wang, Y. ; Kohmoto, J. ; Tokita, D. ; Farver, C. F. ; Tarpey, M. M. ; Billiar, T. R. ; Gladwin, M. T. ; McCurry, K. R. / Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model. In: American Journal of Transplantation. 2012 ; Vol. 12, No. 11. pp. 2938-2948.
@article{246913258a3e453cb0ea6a10a5db97e3,
title = "Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model",
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.",
keywords = "ischemia reperfusion injury, lung transplantation, nitric oxide, Nitrite, rat",
author = "R. Sugimoto and T. Okamoto and Atsunori Nakao and J. Zhan and Y. Wang and J. Kohmoto and D. Tokita and Farver, {C. F.} and Tarpey, {M. M.} and Billiar, {T. R.} and Gladwin, {M. T.} and McCurry, {K. R.}",
year = "2012",
month = "11",
doi = "10.1111/j.1600-6143.2012.04169.x",
language = "English",
volume = "12",
pages = "2938--2948",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Nitrite reduces acute lung injury and improves survival in a rat lung transplantation model

AU - Sugimoto, R.

AU - Okamoto, T.

AU - Nakao, Atsunori

AU - Zhan, J.

AU - Wang, Y.

AU - Kohmoto, J.

AU - Tokita, D.

AU - Farver, C. F.

AU - Tarpey, M. M.

AU - Billiar, T. R.

AU - Gladwin, M. T.

AU - McCurry, K. R.

PY - 2012/11

Y1 - 2012/11

N2 - 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.

AB - 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.

KW - ischemia reperfusion injury

KW - lung transplantation

KW - nitric oxide

KW - Nitrite

KW - rat

UR - http://www.scopus.com/inward/record.url?scp=84868207483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868207483&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2012.04169.x

DO - 10.1111/j.1600-6143.2012.04169.x

M3 - Article

C2 - 23016570

AN - SCOPUS:84868207483

VL - 12

SP - 2938

EP - 2948

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 11

ER -