Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO

Vikas Kapil; Alexandra B. Milsom; Michael Okorie; Sheiva Maleki-Toyserkani; Farihah Akram; Farkhanda Rehman; Shah Arghandawi; Vanessa Pearl; Nigel Benjamin; Stavros Loukogeorgakis; Raymond MacAllister; Adrian J. Hobbs; Andrew Webb; Amrita Ahluwalia

doi:10.1161/HYPERTENSIONAHA.110.153536

Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO

Vikas Kapil, Alexandra B. Milsom, Michael Okorie, Sheiva Maleki-Toyserkani, Farihah Akram, Farkhanda Rehman, Shah Arghandawi, Vanessa Pearl, Nigel Benjamin, Stavros Loukogeorgakis, Raymond MacAllister, Adrian J. Hobbs, Andrew Webb, Amrita Ahluwalia

Research output: Contribution to journal › Article › peer-review

519 Citations (Scopus)

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 (KNO3 capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO3 (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.

Original language	English
Pages (from-to)	274-281
Number of pages	17
Journal	Hypertension
Volume	56
Issue number	2
Early online date	28 Jun 2010
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.110.153536
Publication status	Published - Aug 2010

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10.1161/HYPERTENSIONAHA.110.153536

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Kapil, V., Milsom, A. B., Okorie, M., Maleki-Toyserkani, S., Akram, F., Rehman, F., Arghandawi, S., Pearl, V., Benjamin, N., Loukogeorgakis, S., MacAllister, R., Hobbs, A. J., Webb, A., & Ahluwalia, A. (2010). Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO. Hypertension, 56(2), 274-281. https://doi.org/10.1161/HYPERTENSIONAHA.110.153536

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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 (KNO3 capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO3 (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.",

author = "Vikas Kapil and Milsom, {Alexandra B.} and Michael Okorie and Sheiva Maleki-Toyserkani and Farihah Akram and Farkhanda Rehman and Shah Arghandawi and Vanessa Pearl and Nigel Benjamin and Stavros Loukogeorgakis and Raymond MacAllister and Hobbs, {Adrian J.} and Andrew Webb and Amrita Ahluwalia",

year = "2010",

month = aug,

doi = "10.1161/HYPERTENSIONAHA.110.153536",

language = "English",

volume = "56",

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Kapil, V, Milsom, AB, Okorie, M, Maleki-Toyserkani, S, Akram, F, Rehman, F, Arghandawi, S, Pearl, V, Benjamin, N, Loukogeorgakis, S, MacAllister, R, Hobbs, AJ, Webb, A & Ahluwalia, A 2010, 'Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO', Hypertension, vol. 56, no. 2, pp. 274-281. https://doi.org/10.1161/HYPERTENSIONAHA.110.153536

TY - JOUR

T1 - Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans

T2 - Role for Nitrite-Derived NO

AU - Kapil, Vikas

AU - Milsom, Alexandra B.

AU - Okorie, Michael

AU - Maleki-Toyserkani, Sheiva

AU - Akram, Farihah

AU - Rehman, Farkhanda

AU - Arghandawi, Shah

AU - Pearl, Vanessa

AU - Benjamin, Nigel

AU - Loukogeorgakis, Stavros

AU - MacAllister, Raymond

AU - Hobbs, Adrian J.

AU - Webb, Andrew

AU - Ahluwalia, Amrita

PY - 2010/8

Y1 - 2010/8

N2 - 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 (KNO3 capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO3 (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.

AB - 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 (KNO3 capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO3 (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.

U2 - 10.1161/HYPERTENSIONAHA.110.153536

DO - 10.1161/HYPERTENSIONAHA.110.153536

M3 - Article

SN - 0194-911X

VL - 56

SP - 274

EP - 281

JO - Hypertension

JF - Hypertension

IS - 2

ER -

Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO

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