title: Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO.
abstract: Ingestion of dietary (inorganic) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation. In addition, nitrite is a potent vasodilator in humans, an effect thought to underlie the blood pressure-lowering effects of dietary nitrate (in the form of beetroot juice) ingestion. Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain. Using a randomized crossover study design, we show that nitrate supplementation (KNO(3) capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO(3) (1488 mg of nitrate) versus 24 mmol of KCl [n=20]) or vegetable intake (250 mL of beetroot juice [5.5 mmol nitrate] versus 250 mL of water [n=9]) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure in healthy volunteers. In addition, post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration, whereby blood pressure is decreased in male volunteers, with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers. Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation. In addition, our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women.
authors.affiliation: William Harvey Research Institute, Barts and London Medical School, Queen Mary University of London, London, UK.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kapil
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Milsom
authors.forename: Michael
authors.initials: M
authors.lastname: Okorie
authors.forename: Sheiva
authors.initials: S
authors.lastname: Maleki-Toyserkani
authors.forename: Farihah
authors.initials: F
authors.lastname: Akram
authors.forename: Farkhanda
authors.initials: F
authors.lastname: Rehman
authors.forename: Shah
authors.initials: S
authors.lastname: Arghandawi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pearl
authors.forename: Nigel
authors.initials: N
authors.lastname: Benjamin
authors.forename: Stavros
authors.initials: S
authors.lastname: Loukogeorgakis
authors.forename: Raymond
authors.initials: R
authors.lastname: Macallister
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Hobbs
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Webb
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D001916:Brachial Artery / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D006973:Hypertension / Q000150:complications; D007022:Hypotension / Q000139:chemically induced; D008019:Life Style; D008297:Male; D009566:Nitrates / Q000097:blood / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood / Q000494:pharmacology; D011187:Posture; D011189:Potassium Chloride / Q000494:pharmacology; D017680:Potassium Compounds / Q000494:pharmacology*; D015995:Prevalence; D011897:Random Allocation; D012307:Risk Factors; D012727:Sex Characteristics; D013599:Systole / Q000187:drug effects / Q000502:physiology
chemical_list: D009566:Nitrates; D009573:Nitrites; D017680:Potassium Compounds; D009569:Nitric Oxide; D011189:Potassium Chloride; D006152:Cyclic GMP; C023844:potassium nitrate