Nitric oxide in health and disease of the respiratory system
Open accessAbstract
During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.
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NO activity derived from dietary nitrate and constitutive NOS might be protective against COPD largely through S-nitrosothiol-mediated mechanisms including inhibition of noncholinergic nonadrenergic nerve activity, bronchial smooth muscle relaxation, reduction of airway hyperresponsiveness, downregulation of proinflammatory T lymphocyte activity, and antimicrobial defense.
“NO activity derived from dietary nitrate and constitutive NOS might be protective against COPD largely through the S-nitrosothiol-mediated mechanism including inhibition of the noncholinergic nonadrenergic nerve activity, bronchial smooth muscle relaxation, reduction of airway hyperresponsiveness, downregulation of the proinflammatory activity of T lymphocytes, and antimicrobial defense [127].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [127]
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- Authors
- Ricciardolo, F. L. M., Sterk, P. J., Gaston, B., & Folkerts, G.
- Affiliations
- Utrecht University (NL)
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2004-07
- Volume
- 84
- Issue
- 3
- Pages
- 731-765
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2157430977
- Cited by
- 903
- References
- 485
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 22 · 2023: 26 · 2022: 29 · 2021: 42 · 2020: 31 · 2019: 27 · 2018: 28 · 2017: 42 · 2016: 34 · 2015: 52 · 2014: 48 · 2013: 61 · 2012: 65
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- other-oa
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitric oxide, nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, endothelial nitric oxide synthase, S-nitrosothiols, bronchomotor tone, airway inflammation, asthma, exhaled nitric oxide, reactive nitrogen species, oxidative stress, chronic inflammatory airway diseases, immunomodulation
- MeSH terms
- Administration, Inhalation, Animals, Asthma, Health, Humans, Nitric Oxide, Respiration Disorders, Respiratory System, Respiratory Physiological Phenomena, Oxidative Stress, Exhalation
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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