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Cited by 218Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionBlood Pressure and Hypertension Studies

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

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Ghosh, Suborno M., Kapil, Vikas, Fuentes-Calvo, Isabel, Bubb, Kristen J., Pearl, Vanessa, Milsom, Alexandra B., Khambata, Rayomand, Maleki-Toyserkani, Sheiva, Yousuf, Mubeen, Benjamin, Nigel, Webb, Andrew J., Caulfield, Mark J., Hobbs, Adrian J., Ahluwalia, Amrita·2013·Hypertension
DOI 10.1161/hypertensionaha.111.00933
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Abstract

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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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
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-05
Volume
61
Issue
5
Pages
1091-1102
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.111.00933
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
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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