Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI1378

Nitric oxide synthesis in the lung. Regulation by oxygen through a kinetic mechanism.

R A Dweik, D Laskowski, H M Abu-Soud, F Kaneko, R Hutte, D J Stuehr, and S C Erzurum

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Dweik, R. in: JCI | PubMed | Google Scholar

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Laskowski, D. in: JCI | PubMed | Google Scholar

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Abu-Soud, H. in: JCI | PubMed | Google Scholar

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Kaneko, F. in: JCI | PubMed | Google Scholar

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Hutte, R. in: JCI | PubMed | Google Scholar

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Stuehr, D. in: JCI | PubMed | Google Scholar

Pulmonary and Critical Care Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Find articles by Erzurum, S. in: JCI | PubMed | Google Scholar

Published February 1, 1998 - More info

Published in Volume 101, Issue 3 on February 1, 1998
J Clin Invest. 1998;101(3):660–666. https://doi.org/10.1172/JCI1378.
© 1998 The American Society for Clinical Investigation
Published February 1, 1998 - Version history
View PDF
Abstract

In this study, we show that oxygen regulates nitric oxide (NO) levels through effects on NO synthase (NOS) enzyme kinetics. Initially, NO synthesis in the static lung was measured in bronchiolar gases during an expiratory breath-hold in normal individuals. NO accumulated exponentially to a plateau, indicating balance between NO production and consumption in the lung. Detection of NO2-, NO3-, and S-nitrosothiols in lung epithelial lining fluids confirmed NO consumption by chemical reactions in the lung. Interestingly, alveolar gas NO (estimated from bronchiolar gases at end-expiration) was near zero, suggesting NO in exhaled gases is not derived from circulatory/systemic sources. Dynamic NO levels during tidal breathing in different airway regions (mouth, trachea, bronchus, and bronchiole) were similar. However, in individuals breathing varying levels of inspired oxygen, dynamic NO levels were notably dependent on O2 concentration in the hypoxic range (KmO2 190 microM). Purified NOS type II enzyme activity in vitro was similarly dependent on molecular oxygen levels (KmO2 135 microM), revealing a means by which oxygen concentration affects NO levels in vivo. Based upon these results, we propose that NOS II is a mediator of the vascular response to oxygen in the lung, because its KmO2 allows generation of NO in proportion to the inspired oxygen concentration throughout the physiologic range.

Version history
  • Version 1 (February 1, 1998): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts