Cited by 111Nitric Oxide and Endothelin EffectsHemoglobin structure and functionHeme Oxygenase-1 and Carbon Monoxide

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Heme proteins mediate the conversion of nitrite to nitric oxide in the vascular wall

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Alzawahra, Wael F., Talukder, M. A. Hassan, Liu, Xiaoping, Samouilov, Alexandre, Zweier, Jay L.·2008·American Journal of Physiology-Heart and Circulatory Physiology

DOI 10.1152/ajpheart.00374.2008PMC PMC2519190

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Abstract

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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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)
ORCID: Liu, Xiaoping
Samouilov, Alexandre
Zweier, Jay L.
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
DOI: 10.1152/ajpheart.00374.2008
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 (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › 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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Heme proteins mediate the conversion of nitrite to nitric oxide in the vascular wall

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