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The Biology of Nitrogen Oxides in the Airways
Abstract
Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung. The relationship between the toxicities and the bioactivities of NOx must be understood in the context of their chemical interactions in the pulmonary microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system active in airway epithelial cells, macrophages, neutrophils, mast cells, autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells. The chemical products of NOS in the lung vary with disease states, and are involved in pulmonary neurotransmission, host defense, and airway and vascular smooth muscle relaxation. Further, certain patients with pulmonary hypertension, adult respiratory distress syndrome and asthma may experience physiologic improvement with NOx therapy, including inhalation of nitric oxide (NO.) gas. Both endogenous and exogenous NOx react readily with oxygen, superoxide, water, nucleotides, metalloproteins, thiols, amines, and lipids to form products with biochemical actions ranging from bronchodilation and bacteriostasis (S-nitrosothiols) to cytotoxicity and pulmonary capillary leak (peroxynitrite), as well as those with frank mutagenic potential (nitrosamines). Recent discoveries demonstrating the relevance of these species to the lung have provided new insights into the pathophysiology of pulmonary disease, and they have opened a new horizon of therapeutic possibilities for pulmonary medicine.
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“The hallmark feature of PAH and other forms of PH is reduced bioavailability of NO signaling and poor endothelial responsiveness to triggers of vasodilatation[28–34].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [28]
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Metadata
- Authors
- Gaston, B., Drazen, J. M., Loscalzo, J., & Stamler, J. S.
- Affiliations
- Boston Children's Hospital (US)
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-02-01
- Volume
- 149
- Issue
- 2
- Pages
- 538-551
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2054510493
- Cited by
- 918
- References
- 0
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 4 · 2022: 10 · 2021: 13 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 9 · 2016: 15 · 2015: 16 · 2014: 19 · 2013: 27 · 2012: 16
- FWCI
- 37.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl040411-02, 5p50hl019170-20, 5r01hl043344-04)
- National Heart, Lung, and Blood Institute (HL43344, HL-40411, HL 19170)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- nitrogen oxides, nitric oxide, nitric oxide synthase, airway epithelial cells, S-nitrosothiols, peroxynitrite, nitrosamines, pulmonary hypertension, acute respiratory distress syndrome, asthma, nitric oxide inhalation therapy, bronchodilation, host defense, smooth muscle relaxation
- MeSH terms
- Amino Acid Oxidoreductases, Animals, Humans, Lung, Lung Diseases, Nitric Oxide, Nitrogen Oxides, Nitrous Oxide, Nitric Oxide Synthase
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