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S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.

Publication ,  Journal Article
Moya, MP; Gow, AJ; McMahon, TJ; Toone, EJ; Cheifetz, IM; Goldberg, RN; Stamler, JS
Published in: Proc Natl Acad Sci U S A
May 8, 2001

NO synthases are widely distributed in the lung and are extensively involved in the control of airway and vascular homeostasis. It is recognized, however, that the O(2)-rich environment of the lung may predispose NO toward toxicity. These Janus faces of NO are manifest in recent clinical trials with inhaled NO gas, which has shown therapeutic benefit in some patient populations but increased morbidity in others. In the airways and circulation of humans, most NO bioactivity is packaged in the form of S-nitrosothiols (SNOs), which are relatively resistant to toxic reactions with O(2)/O(2)(-). This finding has led to the proposition that channeling of NO into SNOs may provide a natural defense against lung toxicity. The means to selectively manipulate the SNO pool, however, has not been previously possible. Here we report on a gas, O-nitrosoethanol (ENO), which does not react with O(2) or release NO and which markedly increases the concentration of indigenous species of SNO within airway lining fluid. Inhalation of ENO provided immediate relief from hypoxic pulmonary vasoconstriction without affecting systemic hemodynamics. Further, in a porcine model of lung injury, there was no rebound in cardiopulmonary hemodynamics or fall in oxygenation on stopping the drug (as seen with NO gas), and additionally ENO protected against a decline in cardiac output. Our data suggest that SNOs within the lung serve in matching ventilation to perfusion, and can be manipulated for therapeutic gain. Thus, ENO may be of particular benefit to patients with pulmonary hypertension, hypoxemia, and/or right heart failure, and may offer a new therapeutic approach in disorders such as asthma and cystic fibrosis, where the airways may be depleted of SNOs.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 8, 2001

Volume

98

Issue

10

Start / End Page

5792 / 5797

Location

United States

Related Subject Headings

  • Swine
  • S-Nitrosothiols
  • Respiratory Function Tests
  • Nitroso Compounds
  • Nitric Oxide
  • Mercaptoethanol
  • Lung
  • Hypertension, Pulmonary
  • Gas Chromatography-Mass Spectrometry
  • Animals, Newborn
 

Citation

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Moya, M. P., Gow, A. J., McMahon, T. J., Toone, E. J., Cheifetz, I. M., Goldberg, R. N., & Stamler, J. S. (2001). S-nitrosothiol repletion by an inhaled gas regulates pulmonary function. Proc Natl Acad Sci U S A, 98(10), 5792–5797. https://doi.org/10.1073/pnas.091109498
Moya, M. P., A. J. Gow, T. J. McMahon, E. J. Toone, I. M. Cheifetz, R. N. Goldberg, and J. S. Stamler. “S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.Proc Natl Acad Sci U S A 98, no. 10 (May 8, 2001): 5792–97. https://doi.org/10.1073/pnas.091109498.
Moya MP, Gow AJ, McMahon TJ, Toone EJ, Cheifetz IM, Goldberg RN, et al. S-nitrosothiol repletion by an inhaled gas regulates pulmonary function. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5792–7.
Moya, M. P., et al. “S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.Proc Natl Acad Sci U S A, vol. 98, no. 10, May 2001, pp. 5792–97. Pubmed, doi:10.1073/pnas.091109498.
Moya MP, Gow AJ, McMahon TJ, Toone EJ, Cheifetz IM, Goldberg RN, Stamler JS. S-nitrosothiol repletion by an inhaled gas regulates pulmonary function. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5792–5797.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

May 8, 2001

Volume

98

Issue

10

Start / End Page

5792 / 5797

Location

United States

Related Subject Headings

  • Swine
  • S-Nitrosothiols
  • Respiratory Function Tests
  • Nitroso Compounds
  • Nitric Oxide
  • Mercaptoethanol
  • Lung
  • Hypertension, Pulmonary
  • Gas Chromatography-Mass Spectrometry
  • Animals, Newborn