Mechanisms of nitrite reduction to nitric oxide in the heart and vessel wall
Open accessAbstract
Nitric oxide (NO) is an important regulator of a variety of biological functions, and also has a role in the pathogenesis of cellular injury. It had been generally accepted that NO is solely generated in biological tissues by specific nitric oxide synthases (NOS) which metabolize arginine to citrulline with the formation of NO. However, over the last 15 years, nitrite-mediated NO production has been shown to be an important mechanism of NO formation in the heart and cardiovascular system. Now numerous studies have demonstrated that nitrite can be an important source rather than simply a product of NO in mammalian cells and tissues and can be a potential vasodilator drug for cardiovascular diseases. There are a variety of mechanisms of nitrite reduction to NO and it is now appreciated that this process, while enhanced under hypoxic conditions, also occurs under normoxia. Several methods, including electron paramagnetic resonance, chemiluminescence NO analyzer, and NO electrode have been utilized to measure, quantitate, and image nitrite-mediated NO formation. Results reveal that nitrite-dependent NO generation plays critical physiological and pathological roles, and is controlled by oxygen tension, pH, reducing substrates and nitrite levels. In this manuscript, we review the mechanisms of nitrite-mediated NO formation and the effects of oxygen on this process with a focus on how this occurs in the heart and vessels.
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NOS-independent nitric oxide generation from nitrite occurs in the ischemic heart.
“A year later, Zweier et al. demonstrated NOS-independent nitric oxide generation from nitrite in the ischemic heart, thereby extending the occurrence of nitrite reduction outside the gastrointestinal tract.11”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [11]
The Zn/S cluster is particularly sensitive to peroxynitrite.
“Work by Zou et al. indicated that this cluster is particularly sensitive to peroxynitrite (1070).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1070]
These findings are consistent with previous observations that nitrite may be converted to NO in tissues and in blood, particularly in states of hypoxia and acidosis.
“These findings are consistent with previous observations that nitrite may be converted to NO in tissues and in blood, particularly in states of hypoxia and acidosis (12,13).”
From Dietary nitrate, nitric oxide, and restenosis (2011) · cites this paper as [13]
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- Authors
- Zweier, J. L., Li, H., Samouilov, A., & Liu, X.
- Affiliations
- The Ohio State University Wexner Medical Center (US)
- Corresponding author
- Zweier, Jay L.
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 22
- Issue
- 2
- Pages
- 83-90
- ISSN
- 1089-8603 (ISSN-L)
- PMC
- PMC2851168
- OpenAlex
- W2024487462
- Cited by
- 132
- References
- 70
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 9 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 15 · 2012: 10
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL063744, P01HL065608, R01HL038324)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- nitrite reduction, heart, vascular wall, hypoxia, oxygen partial pressure, pH, nitric oxide synthase, vasodilators, cardiovascular disease
- MeSH terms
- Animals, Blood Vessels, Heart, Humans, Nitric Oxide, Nitrites, Oxidation-Reduction
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