Antiplatelet effects of dietary nitrate in healthy volunteers: involvement of cGMP and influence of sex
Velmurugan S, Kapil V, Ghosh SM, Davies S, McKnight A, Aboud Z, Khambata RS, Webb AJ, Poole A, Ahluwalia A
Free radical biology & medicine · 98 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
- Intake measured by
- Not stated
Who paid for it
- Funding
- Independent funding
- Nonprofit
- British Heart Foundation
- Government
- Medical Research Council
- Authors
- At least one author declares a financial tie to industry
- Grants
- British Heart Foundation (FS/11/41/28749)
Based on 2 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2013-06-25 · Free Radic Biol Med · vol. 65 · pp. 1521–1532
- Publisher
- Elsevier BV
- Cited
- 114 citations · more than 98% of similar papers · 7.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 62 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Nitric Oxide and Endothelin Effects · Antiplatelet Therapy and Cardiovascular Diseases · Cardiovascular Syncope and Autonomic Disorders
- Keywords
- Nitrate, Ingestion, Platelet, Nitrite, Crossover study, Placebo, Epinephrine, Chemistry, Internal medicine, Platelet activation, Potassium nitrate, Endocrinology, Medicine, Potassium
- MeSH
- blood platelets, erythrocytes, humans, beta vulgaris, vegetables, cardiovascular diseases, nitrates, nitric oxide, potassium compounds, epinephrine, collagen, guanylate cyclase, p-selectin, cyclic gmp, platelet aggregation inhibitors, diet, cross-over studies, sex factors, platelet aggregation, dietary supplements, adolescent, adult, middle aged, female, male, young adult
10 authors
From GB
- Shanti VelmuruganQueen Mary University of London; William Harvey Research Institute
- Vikas KapilQueen Mary University of London; William Harvey Research Institute
- Suborno M. GhoshQueen Mary University of London; William Harvey Research Institute
- Sheridan DaviesQueen Mary University of London; William Harvey Research Institute
- Andrew McKnightQueen Mary University of London; William Harvey Research Institute
- Zainab AboudQueen Mary University of London; William Harvey Research Institute
Abstract
Ingestion of vegetables rich in inorganic nitrate has emerged as an effective method, via the formation of a nitrite intermediate, for acutely elevating vascular NO levels. As such a number of beneficial effects of dietary nitrate ingestion have been demonstrated including the suggestion that platelet reactivity is reduced. In this study we investigated whether inorganic nitrate supplementation might also reduce platelet reactivity in healthy volunteers and have determined the mechanisms involved in the effects seen. We conducted two randomised crossover studies each in 24 (12 of each sex) healthy subjects assessing the acute effects of dietary nitrate (250 ml beetroot juice) or potassium nitrate capsules (KNO3, 8 mmol) vs placebo control on platelet reactivity. Inorganic nitrate ingested either from a dietary source or via supplementation raised circulating nitrate and nitrite levels in both sexes and attenuated ex vivo platelet aggregation responses to ADP and, albeit to a lesser extent, collagen but not epinephrine in male but not female volunteers. These inhibitory effects were associated with a reduced platelet P-selectin expression and elevated platelet cGMP levels. In addition, we show that nitrite reduction to NO occurs at the level of the erythrocyte and not the platelet. In summary, our results demonstrate that inorganic nitrate ingestion, whether via the diet or through supplementation, causes a modest decrease in platelet reactivity in healthy males but not females. Our studies provide strong support for further clinical trials investigating the potential of dietary nitrate as an adjunct to current antiplatelet therapies to prevent atherothrombotic complications. Moreover, our observations highlight a previously unknown sexual dimorphism in platelet reactivity to NO and intimate a greater dependence of males on the NO-soluble guanylate cyclase pathway in limiting thrombotic potential.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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