The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Enhanced Vasodilator Activity of Nitrite in Hypertension: Critical Role for Erythrocytic Xanthine Oxidoreductase and Translational Potential
Open accessAbstract
Elevation of circulating nitrite (NO 2 − ) levels causes vasodilatation and lowers blood pressure in healthy volunteers. Whether these effects and the underpinning mechanisms persist in hypertension is unknown. Therefore, we investigated the consequences of systemic nitrite elevation in spontaneously hypertensive rats and conducted proof-of-principle studies in patients. Nitrite caused dose-dependent blood pressure–lowering that was profoundly enhanced in spontaneously hypertensive rats versus normotensive Wistar Kyoto controls. This effect was virtually abolished by the xanthine oxidoreductase (XOR) inhibitor, allopurinol, and associated with hypertension-specific XOR-dependent nitrite reductase activity localized to the erythrocyte but not the blood vessel wall. To determine whether these pathways translate to human hypertension, we investigated the effects of elevation of circulating nitrite levels in 15 drug naïve grade 1 hypertensives. To elevate nitrite, we used a dose of dietary nitrate (≈3.5 mmol) that elevated nitrite levels ≈1.5-fold ( P <0.01); a rise shown previously to exert no significant blood pressure–lowering effects in normotensives. This dose caused substantial reductions in systolic (≈12 mm Hg) and diastolic blood pressures ( P <0.001) and pulse wave velocity ( P <0.05); effects associated with elevations in erythrocytic XOR expression and XOR-dependent nitrite reductase activity. Our observations demonstrate the improved efficacy of inorganic nitrate and nitrite in hypertension as a consequence of increased erythrocytic XOR nitrite reductase activity and support the concept of dietary nitrate supplementation as an effective, but simple and inexpensive, antihypertensive strategy.
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Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
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Self-citationRed Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia
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“Other proposed nitrite reductases catalyzing NO formation from nitrite under hypoxic conditions are carbonic anhydrase (1), xanthine oxidase (68), or eNOS (189), which are all present in RBCs.”
Xanthine Oxidoreductase‐Derived Reactive Species: Physiological and Pathological Effects
Battelli, M. G., Polito, L., Bortolotti, M., & Bolognesi, A. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3527579 · Cited by 281
“This effect is related to an increased NO generation, which is significantly attenuated by allopurinol and is associated with higher levels of erythrocytic XOR expression and nitrite reductase activity in hypertensive patients in comparison to normotensives volunteers [42].”
Background
Metadata
- Authors
- Ghosh, S. M., Kapil, V., Fuentes-Calvo, I., Bubb, K. J., Pearl, V., Milsom, A. B., Khambata, R., Maleki-Toyserkani, S., Yousuf, M., Benjamin, N., Webb, A. J., Caulfield, M. J., Hobbs, A. J., & Ahluwalia, A.
- Affiliations
- Queen Mary University of London (GB)
- From the William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom (S.M.G., V.K., I.F.-C., K.J.B., V.P., A.B.M., R.K., S.M-T., M.Y., M.J.C., A.J.H., A.A.); IBSAL-Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain (I.F.-C.); University of Exeter Medical School, Exeter, United Kingdom (N.B.); and Clinical Pharmacology, King’s College London, London, United Kingdom (A.J.W.).
- ORCID
- Venue
- Hypertension
- Published
- 2013-05
- Volume
- 61
- Issue
- 5
- Pages
- 1091-1102
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2100756743
- Cited by
- 218
- References
- 61
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 16 · 2023: 14 · 2022: 15 · 2021: 13 · 2020: 14 · 2019: 15 · 2018: 16 · 2017: 17 · 2016: 23 · 2015: 26 · 2014: 25 · 2013: 13
- FWCI
- 20.14
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- other-oa
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (NF-SI-0512-10113)
- British Heart Foundation (SP/08/006/25110, SP08006)
- National Institutes of Health
- Medical Research Council (MR/K006584/1)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- nitrite, nitrate supplementation, xanthine oxidoreductase, nitrite reductase, erythrocytes, vasodilation, blood pressure reduction, pulse wave velocity, allopurinol, spontaneously hypertensive rats, nitric oxide
- MeSH terms
- Allopurinol, Animals, Blood Pressure, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Erythrocytes, Female, Humans, Hypertension, Male, Middle Aged, Nitrites, Rats, Inbred SHR, Rats, Inbred WKY, Vasodilation, Xanthine Dehydrogenase, Signal Transduction, Cross-Over Studies, Rats, Translational Research, Biomedical
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