S-nitrosothiol repletion by an inhaled gas regulates pulmonary function

Martin P. Moya, Andrew J. Gow, Timothy J. McMahon, Eric J. Toone, Ira M. Cheifetz, Ronald N. Goldberg, Jonathan S. Stamler

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 O2-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-nitro-sothiols (SNOs), which are relatively resistant to toxic reactions with O2/O2 -. 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 O2 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.

Original languageEnglish
Pages (from-to)5792-5797
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number10
DOIs
Publication statusPublished - 8 May 2001
Externally publishedYes

Fingerprint

S-Nitrosothiols
Gases
Lung
Hemodynamics
Airway Management
Poisons
Lung Injury
Vasoconstriction
Pulmonary Hypertension
Cystic Fibrosis
Nitric Oxide Synthase
Cardiac Output
Inhalation
Blood Vessels
Ventilation
Homeostasis
Swine
Therapeutics
Asthma
Heart Failure

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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. Proceedings of the National Academy of Sciences of the United States of America, 98(10), 5792-5797. https://doi.org/10.1073/pnas.091109498

S-nitrosothiol repletion by an inhaled gas regulates pulmonary function. / Moya, Martin P.; Gow, Andrew J.; McMahon, Timothy J.; Toone, Eric J.; Cheifetz, Ira M.; Goldberg, Ronald N.; Stamler, Jonathan S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 10, 08.05.2001, p. 5792-5797.

Research output: Contribution to journalArticle

Moya, MP, Gow, AJ, McMahon, TJ, Toone, EJ, Cheifetz, IM, Goldberg, RN & Stamler, JS 2001, 'S-nitrosothiol repletion by an inhaled gas regulates pulmonary function', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 10, pp. 5792-5797. https://doi.org/10.1073/pnas.091109498
Moya, Martin P. ; Gow, Andrew J. ; McMahon, Timothy J. ; Toone, Eric J. ; Cheifetz, Ira M. ; Goldberg, Ronald N. ; Stamler, Jonathan S. / S-nitrosothiol repletion by an inhaled gas regulates pulmonary function. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 10. pp. 5792-5797.
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