Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function
Open accessAbstract
Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO₂⁻) and nitrate (NO₃⁻) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseases. We have previously shown that nitrite anions at 0.1 µM inhibit aggregation and activation of human platelet preparations in vitro in the presence of red blood cells and this effect was enhanced by deoxygenation, an effect likely due to NO generation. In the present study, we hypothesized that nitrite and nitrate derived from the diet could also alter platelet function upon their conversion to NO in vivo. To manipulate the levels of nitrite and nitrate in mouse blood, we used antibiotics, NOS inhibitors, low nitrite/nitrate (NOx) diets, endothelial NOS knock-out mice and also supplementation with high levels of nitrite or nitrate in the drinking water. We found that all of these perturbations affected nitrite and nitrate levels but that the lowest whole blood values were obtained by dietary restriction. Platelet aggregation and ATP release were measured in whole blood and the results show an inverse correlation between nitrite/nitrate levels and platelet activity in aggregation and ATP release. Furthermore, we demonstrated that nitrite-supplemented group has a prolonged bleeding time compared with control or low NOx diet group. These results show that diet restriction contributes greatly to blood nitrite and nitrate levels and that platelet reactivity can be significantly affected by these manipulations. Our study suggests that endogenous levels of nitrite and nitrate may be used as a biomarker for predicting platelet function and that dietary manipulation may affect thrombotic processes.
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RBC-mediated nitrite reduction and subsequent inhibition of platelet aggregation do not take place with nitrite alone.
“The latest hypothesis is supported by the fact that RBC-mediated nitrite reduction and subsequent inhibition of platelet (PLT) aggregation do not take place with nitrite alone (2, 144).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [144]
Nitrite decreases platelet activation.
“In addition, nitrite has been shown to decrease platelet activation [11, 12].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [12]
Nitrite has also been shown to decrease platelet activation and aggregation.
“Nitrite has also been shown to decrease platelet activation and aggregation [11, 12].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [12]
Dietary restriction of nitrite and nitrate in a murine model led to reduced platelet aggregation and activity.
“Dietary restriction of nitrite and nitrate in a murine model led to reduced platelet aggregation and activity”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [12]
Supplementation with nitrite or nitrate inhibited platelet aggregation in a murine model.
“while supplementation with nitrite or nitrate inhibited platelet aggregation [12].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [12]
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- Authors
- Park, J. W., Piknova, B., Huang, P. L., Noguchi, C. T., & Schechter, A. N.
- Affiliations
- National Institutes of Health (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Schechter, Alan N.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-02-01
- Volume
- 8
- Issue
- 2
- Pages
- e55699
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3562242
- OpenAlex
- W2063092400
- Cited by
- 82
- References
- 42
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 6 · 2014: 14 · 2013: 8
- FWCI
- 8.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- nitric oxide, platelet function, platelet aggregation, ATP release, endothelial nitric oxide synthase, bleeding time, thrombosis, hemostasis, nitrite supplementation
- MeSH terms
- Adenosine Triphosphate, Analysis of Variance, Animals, Blood Platelets, Luminescent Measurements, Mice, Inbred C57BL, Nitrates, Nitrites, Platelet Aggregation, Biomarkers, Mice, Knockout, Dietary Supplements, Mice, Nitric Oxide Synthase Type III
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