Nitrates: another mistake of environmentalists?

• The main interest of this paper is beet juice for hypertension!
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• Original Article

Enhanced Vasodilator Activity of Nitrite in Hypertension

Critical Role for Erythrocytic Xanthine Oxidoreductase and Translational Potential

1. Suborno M. Ghosh*, 
2. Vikas Kapil*, 
3. Isabel Fuentes-Calvo*,
4. Kristen J. Bubb, 
5. Vanessa Pearl, 
6. Alexandra B. Milsom,
7. Rayomand Khambata, 
8. Sheiva Maleki-Toyserkani, 
9. Mubeen Yousuf,
10. Nigel Benjamin, 
11. Andrew J. Webb, 
12. Mark J. Caulfield, 
13. Adrian J. Hobbs,
14. Amrita Ahluwalia

+Author Affiliations

1. 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.).

1. Correspondence to Amrita Ahluwalia, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom. E-mail a.ahluwalia@qmul.ac.uk

1. ↵* S.M.G., V.K., and I.F.-C. contributed equally to this article.

Abstract

Elevation of circulating nitrite (NO₂⁻) 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="" and="" blood="" caused="" diastolic="" dose="" effects="" em="" exert="" hg="" in="" lowering="" mm="" no="" normotensives.="" pressure="" pressures="" previously="" reductions="" rise="" shown="" significant="" style="border: 0px; font-family: inherit; font-size: inherit; line-height: inherit; margin: 0px; outline-style: none; padding: 0px; text-align: inherit; vertical-align: baseline;" substantial="" systolic="" this="" to="">P

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