title: Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite.
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 (Delta(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.
authors.affiliation: Clinical Pharmacology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Webb
authors.forename: Nakul
authors.initials: N
authors.lastname: Patel
authors.forename: Stavros
authors.initials: S
authors.lastname: Loukogeorgakis
authors.forename: Mike
authors.initials: M
authors.lastname: Okorie
authors.forename: Zainab
authors.initials: Z
authors.lastname: Aboud
authors.forename: Shivani
authors.initials: S
authors.lastname: Misra
authors.forename: Rahim
authors.initials: R
authors.lastname: Rashid
authors.forename: Philip
authors.initials: P
authors.lastname: Miall
authors.forename: John
authors.initials: J
authors.lastname: Deanfield
authors.forename: Nigel
authors.initials: N
authors.lastname: Benjamin
authors.forename: Raymond
authors.initials: R
authors.lastname: MacAllister
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Hobbs
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D000293:Adolescent; D000328:Adult; D027461:Beta vulgaris; D001794:Blood Pressure / Q000502:physiology*; D018592:Cross-Over Studies; D004032:Diet; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D010974:Platelet Aggregation / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D012463:Saliva / Q000378:metabolism; D014059:Tongue / Q000382:microbiology
chemical_list: D009566:Nitrates; D009573:Nitrites