Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways

Benjamin Gaston, John Reilly, Jeffrey M. Drazen, James Fackler, Pranai Ramdev, Derrick Arnelle, Mark E. Mullins, David J. Sugarbaker, Cynthia Chee, David J. Singel, Joseph Loscalzo, Jonathan S. Stamler

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Recent discoveries suggesting essential bioactivities of nitric oxide (NȮ) in the lung are difficult to reconcile with the established pulmonary cytotoxicity of this common air pollutant. These conflicting observations suggest that metabolic intermediaries may exist in the lung to modulate the bioactivity and toxicity of NȮ. We report that S-nitrosothiols (RS-NO), predominantly the adduct with glutathione, are present at nano- to micromolar concentrations in the airways of normal subjects and that their levels vary in different human pathophysiologic states. These endogenous RS-NO are long-lived, potent relaxants of human airways under physiological O2 concentrations. Moreover, RS-NO form in high concentrations upon administration of NȮ gas. Nitrite (10-20 μM) is found in airway lining fluid in concentrations linearly proportional to leukocyte counts, suggestive of local NȮ metabolism. NȮ itself was not detected either free in solution or in complexes with transition metals. These observations may provide insight into the means by which NȮ is packaged in biological systems to preserve its bioactivity and limit its potential O2-dependent toxicity and suggest an important role for NȮ in regulation of airway luminal homeostasis.

Original languageEnglish (US)
Pages (from-to)10957-10961
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Dec 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • General


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