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Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects.

Publication ,  Journal Article
Demchenko, IT; Atochin, DN; Gutsaeva, DR; Godfrey, RR; Huang, PL; Piantadosi, CA; Allen, BW
Published in: Am J Physiol Lung Cell Mol Physiol
May 2008

Reactive species of oxygen and nitrogen have been collectively implicated in pulmonary oxygen toxicity, but the contributions of specific molecules are unknown. Therefore, we assessed the roles of several reactive species, particularly nitric oxide, in pulmonary injury by exposing wild-type mice and seven groups of genetically altered mice to >98% O2 at 1, 3, or 4 atmospheres absolute. Genetically altered animals included knockouts lacking either neuronal nitric oxide synthase (nNOS(-/-)), endothelial nitric oxide synthase (eNOS(-/-)), inducible nitric oxide synthase (iNOS(-/-)), extracellular superoxide dismutase (SOD3(-/-)), or glutathione peroxidase 1 (GPx1(-/-)), as well as two transgenic variants (S1179A and S1179D) having altered eNOS activities. We confirmed our earlier finding that normobaric hyperoxia (NBO2) and hyperbaric hyperoxia (HBO2) result in at least two distinct but overlapping patterns of pulmonary injury. Our new findings are that the role of nitric oxide in the pulmonary pathophysiology of hyperoxia depends both on the specific NOS isozyme that is its source and on the level of hyperoxia. Thus, iNOS predominates in the etiology of lung injury in NBO2, and SOD3 provides an important defense. But in HBO2, nNOS is a major contributor to pulmonary injury, whereas eNOS is protective. In addition, we demonstrated that nitric oxide derived from nNOS is involved in a neurogenic mechanism of HBO2-induced lung injury that is linked to central nervous system oxygen toxicity through adrenergic/cholinergic pathways.

Duke Scholars

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

ISSN

1040-0605

Publication Date

May 2008

Volume

294

Issue

5

Start / End Page

L984 / L990

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Respiratory System
  • Oxyhemoglobins
  • Oxygen
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type I
  • Nitric Oxide
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Demchenko, I. T., Atochin, D. N., Gutsaeva, D. R., Godfrey, R. R., Huang, P. L., Piantadosi, C. A., & Allen, B. W. (2008). Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects. Am J Physiol Lung Cell Mol Physiol, 294(5), L984–L990. https://doi.org/10.1152/ajplung.00420.2007
Demchenko, Ivan T., Dmitriy N. Atochin, Diana R. Gutsaeva, Ryan R. Godfrey, Paul L. Huang, Claude A. Piantadosi, and Barry W. Allen. “Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects.Am J Physiol Lung Cell Mol Physiol 294, no. 5 (May 2008): L984–90. https://doi.org/10.1152/ajplung.00420.2007.
Demchenko IT, Atochin DN, Gutsaeva DR, Godfrey RR, Huang PL, Piantadosi CA, et al. Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects. Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L984–90.
Demchenko, Ivan T., et al. “Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects.Am J Physiol Lung Cell Mol Physiol, vol. 294, no. 5, May 2008, pp. L984–90. Pubmed, doi:10.1152/ajplung.00420.2007.
Demchenko IT, Atochin DN, Gutsaeva DR, Godfrey RR, Huang PL, Piantadosi CA, Allen BW. Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects. Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L984–L990.

Published In

Am J Physiol Lung Cell Mol Physiol

DOI

ISSN

1040-0605

Publication Date

May 2008

Volume

294

Issue

5

Start / End Page

L984 / L990

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Respiratory System
  • Oxyhemoglobins
  • Oxygen
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type I
  • Nitric Oxide
  • Mice, Mutant Strains
  • Mice, Inbred C57BL