Heme proteins mediate the conversion of nitrite to nitric oxide in the vascular wall
Open accessAbstract
Nitric oxide (NO) has been shown to be the endothelium-derived relaxing factor (EDRF), and its impairment contributes to a variety of cardiovascular disorders. Recently, it has been recognized that nitrite can be an important source of NO; however, questions remain regarding the activity and mechanisms of nitrite bioactivation in vessels and its physiological importance. Therefore, we investigated the effects of nitrite on in vivo hemodynamics in rats and in vitro vasorelaxation in isolated rat aorta under aerobic conditions. Studies were performed to determine the mechanisms by which nitrite is converted to NO. In anesthetized rats, nitrite dose dependently decreased both systolic and diastolic blood pressure with a threshold dose of 10 μM. Similarly, nitrite (10 μM-2 mM) caused vasorelaxation of aortic rings, and NO was shown to be the intermediate factor responsible for this activity. With the use of electrochemical as well as electron paramagnetic resonance (EPR) spectroscopy techniques NO generation was measured from isolated aortic vessels following nitrite treatment. Reduction of nitrite to NO was blocked by heating the vessel, suggesting that an enzymatic process is involved. Organ chamber experiments demonstrated that aortic relaxation induced by nitrite could be blocked by both hemoglobin and soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). In addition, both electrochemical and EPR spin-trapping measurements showed that ODQ inhibits nitrite-mediated NO production. These findings thus suggest that nitrite can be a precursor of EDRF and that sGC or other heme proteins inhibited by ODQ catalyze the reduction of nitrite to NO.
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Nitrite reduction is mediated by complementary systems including deoxyhaemoglobin, deoxymyoglobin, xanthine oxidoreductase, and mitochondrial enzymes.
“This reduction is mediated by complementary systems, including deoxyhaemoglobin, deoxymyoglobin, xanthine oxidoreductase, and mitochondrial enzymes [54,55,56].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [54]
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- Authors
- Alzawahra, W. F., Talukder, M. A. H., Liu, X., Samouilov, A., & Zweier, J. L.
- Affiliations
- The Ohio State University (US)
- The Ohio State University Wexner Medical Center (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2008-08
- Volume
- 295
- Issue
- 2
- Pages
- H499-H508
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC2519190
- OpenAlex
- W2111609140
- Cited by
- 111
- References
- 65
- Citations by year
- 2026: 2 · 2025: 1 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 11 · 2014: 11 · 2013: 4 · 2012: 20
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-38324, R01HL063744, HL 65608, P01HL065608, HL 63744)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- nitrite, nitric oxide, heme proteins, endothelium-derived relaxing factor, soluble guanylate cyclase, hemoglobin, vasorelaxation, aorta, blood pressure, ODQ, spin trapping, cardiovascular physiology
- MeSH terms
- Soluble Guanylyl Cyclase, Animals, Aorta, Thoracic, Blood Pressure, Dose-Response Relationship, Drug, Electrochemistry, Electron Spin Resonance Spectroscopy, Enzyme Inhibitors, Guanylate Cyclase, Heart Rate, Hemeproteins, Infusions, Intravenous, Male, Nitric Oxide, Nitrites, Oxadiazoles, Oxyhemoglobins, Quinoxalines, Vasodilation, Signal Transduction, Rats, Sprague-Dawley, Receptors, Cytoplasmic and Nuclear, Endothelium-Dependent Relaxing Factors, Rats, In Vitro Techniques
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