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Nitrite confers protection against myocardial infarction: Role of xanthine oxidoreductase, NADPH oxidase and KATP channels
Open accessAbstract
Reduction of nitrite to nitric oxide during ischemia protects the heart against injury from ischemia/reperfusion. However the optimal dose of nitrite and the mechanisms underlying nitrite-induced cardioprotection are not known. We determined the ability of nitrite and nitrate to confer protection against myocardial infarction in two rat models of ischemia/reperfusion injury and the role of xanthine oxidoreductase, NADPH oxidase, nitric oxide synthase and K(ATP) channels in mediating nitrite-induced cardioprotection. In vivo and in vitro rat models of myocardial ischemia/reperfusion injury were used to cause infarction. Hearts (n=6/group) were treated with nitrite or nitrate for 15 min prior to 30 min regional ischemia and 180 min reperfusion. Xanthine oxidoreductase activity was measured after 15 min aerobic perfusion and 30 min ischemia. Nitrite reduced myocardial necrosis and decline in ventricular function following ischemia/reperfusion in the intact and isolated rat heart in a dose- or concentration-dependent manner with an optimal dose of 4 mg/kg in vivo and concentration of 10 microM in vitro. Nitrate had no effect on protection. Reduction in infarction by nitrite was abolished by the inhibition of flavoprotein reductases and the molybdenum site of xanthine oxidoreductase and was associated with an increase in activity of xanthine dehydrogenase and xanthine oxidase during ischemia. Inhibition of nitric oxide synthase had no effect on nitrite-induced cardioprotection. Inhibition of NADPH oxidase and K(ATP) channels abolished nitrite-induced cardioprotection. Nitrite but not nitrate protects against infarction by a mechanism involving xanthine oxidoreductase, NADPH oxidase and K(ATP) channels.
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In the citing paper
“the nitrate/nitrite content of the fruits and vegetables could contribute to their cardiovascular health benefits in animals [29,33,78,79,80,81,82,83] and humans [31,84,85,86].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [81]
In the citing paper
“The efficacy of low concentrations of nitrite in mediating cytoprotection has been demonstrated in a variety of tissues in animal models including heart [8, 9, 55, 118–122] liver [9, 120, 123], brain [124–126], kidney [127, 128], hindlimb [129], and human forearm [23].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [118]
In the citing paper
“Numerous studies have suggested that nitrite-mediated cytoprotection is mediated by NO production from the molybdenum containing enzyme XOR [8, 39, 86, 118, 127] and to some extent SO [39] as well.”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [118]
In the citing paper
“and also showed that XOR inhibition abolished the protective effect of nitrite in perfused rate heart models [118].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [118]
In the citing paper
“Nitrite was shown to be protective in a rat in vivo model of myocardial IR”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [118]
In the citing paper
“pretreatment with this compound, delivered as a salt in the form of sodium nitrite, protects against ischemia/reperfusion (I/R) injury in the heart in preclinical models (7, 19, 20, 40, 46, 60, 79, 189).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [7]
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Metadata
- Authors
- Baker, J. E., Su, J., Fu, X., Hsu, A., Gross, G. J., Tweddell, J. S., & Hogg, N.
- Affiliations
- Children's Hospital of Wisconsin (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Baker, John E.
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 43
- Issue
- 4
- Pages
- 437-444
- ISSN
- 0022-2828 (ISSN-L)
- PMC
- PMC2735077
- OpenAlex
- W2079200111
- Cited by
- 137
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 11 · 2016: 4 · 2015: 14 · 2014: 12 · 2013: 14 · 2012: 5
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
- Keywords
- nitrite, nitrate, myocardial infarction, ischemia-reperfusion injury, cardioprotection, xanthine oxidoreductase, NADPH oxidase, ATP-sensitive potassium channels, nitric oxide, flavoprotein reductase, xanthine dehydrogenase, xanthine oxidase, nitric oxide synthase, myocardial necrosis, ventricular function
- MeSH terms
- Animals, Cardiotonic Agents, Dose-Response Relationship, Drug, Male, Myocardial Infarction, Nitrates, Nitric Oxide, Nitrites, Time Factors, Xanthine Dehydrogenase, Rats, Sprague-Dawley, NADPH Oxidases, Rats, KATP Channels
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