Published Online
on February 4, 2008

A more recent version of this article appeared on March 1, 2008

This Article Full Text (PDF) CME: Take the course for this article: Hypertension: March 2008, Volume 51, Number 3 Data Supplement All Versions of this Article: 51/3/784    most recent HYPERTENSIONAHA.107.103523v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Webb, A. J. Articles by Ahluwalia, A. Search for Related Content PubMed PubMed Citation Articles by Webb, A. J. Articles by Ahluwalia, A. Related Collections Cardiovascular Pharmacology Hypertension - basic studies Aggregation Clinical Studies Other Treatment Endothelium/vascular type/nitric oxide Other Vascular biology Related Article

Submitted on October 16, 2007
Revised on November 10, 2007

Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite

Andrew J. Webb; Nakul Patel; Stavros Loukogeorgakis; Mike Okorie; Zainab Aboud; Shivani Misra; Rahim Rashid; Philip Miall; John Deanfield; Nigel Benjamin; Raymond MacAllister; Adrian J. Hobbs; and Amrita Ahluwalia^*

From Clinical Pharmacology (A.J.W., N.P., Z.A., S.M., R.R., A.A.), William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University, London, UK; Clinical Pharmacology (S.L., M.O., R.M.), The Rayne Institute, University College London, UK; Clinical Biochemistry (P.M.), William Harvey Research Institutes Barts & the London School of Medicine and Dentistry, London, UK; the Institute of Child Health (J.D.), University College London, UK; Peninsula Medical School (N.B.), Tamar Science Park, Plymouth UK; and the Wolfson Institute for Biomedical Research (A.J.H.), University College London, UK.

^* To whom correspondence should be addressed. E-mail: a.ahluwalia{at}qmul.ac.uk.

Abstract—Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (_max -10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a "natural" low cost approach for the treatment of cardiovascular disease.

Key words: diet • nitric oxide • blood pressure • hypertension • ischemia/reperfusion • platelets • endothelium

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