Cited by 109Platelet Disorders and TreatmentsNitric Oxide and Endothelin EffectsBlood Coagulation and Thrombosis Mechanisms

Platelet Inhibition by Nitrite Is Dependent on Erythrocytes and Deoxygenation

Open access
Srihirun, Sirada, Sriwantana, Thanaporn, Unchern, Supeenun, Kittikool, Dusadee, Noulsri, Egarit, Pattanapanyasat, Kovit, Fucharoen, Suthat, Piknova, Barbora +2 more·2012·PLoS ONE

Abstract

BACKGROUND: Nitrite is a nitric oxide (NO) metabolite in tissues and blood, which can be converted to NO under hypoxia to facilitate tissue perfusion. Although nitrite is known to cause vasodilation following its reduction to NO, the effect of nitrite on platelet activity remains unclear. In this study, the effect of nitrite and nitrite+erythrocytes, with and without deoxygenation, on platelet activity was investigated. METHODOLOGY/FINDING: Platelet aggregation was studied in platelet-rich plasma (PRP) and PRP+erythrocytes by turbidimetric and impedance aggregometry, respectively. In PRP, DEANONOate inhibited platelet aggregation induced by ADP while nitrite had no effect on platelets. In PRP+erythrocytes, the inhibitory effect of DEANONOate on platelets decreased whereas nitrite at physiologic concentration (0.1 µM) inhibited platelet aggregation and ATP release. The effect of nitrite+erythrocytes on platelets was abrogated by C-PTIO (a membrane-impermeable NO scavenger), suggesting an NO-mediated action. Furthermore, deoxygenation enhanced the effect of nitrite as observed from a decrease of P-selectin expression and increase of the cGMP levels in platelets. The ADP-induced platelet aggregation in whole blood showed inverse correlations with the nitrite levels in whole blood and erythrocytes. CONCLUSION: Nitrite alone at physiological levels has no effect on platelets in plasma. Nitrite in the presence of erythrocytes inhibits platelets through its reduction to NO, which is promoted by deoxygenation. Nitrite may have role in modulating platelet activity in the circulation, especially during hypoxia.

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Crossref · 10.1371/journal.pone.0030380

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  • In the context of atherosclerosis, HOCl has been shown to oxidize both high and low density lipoproteins.

    “In the context of atherosclerosis, HOCl has been shown to oxidize both high and low density lipoproteins (90, 470, 881, 1042).”
  • 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 [11]

  • 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 [11]

  • The effect of nitrite on platelet activation in the presence of erythrocytes was abrogated in the presence of the NO scavenger C-PTIO.

    “and abrogated in the presence of the NO scavenger C-PTIO (Figure 7) [115].”

    From Mechanisms of nitrite bioactivation (2014) · cites this paper as [115]

  • Erythrocytes can export NO bioactivity from nitrite.

    “These data support the notion that erythrocytes can export NO bioactivity from nitrite.”

    From Mechanisms of nitrite bioactivation (2014) · cites this paper as [11]

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References 34 · Cited by 109

Authors
Srihirun, S., Sriwantana, T., Unchern, S., Kittikool, D., Noulsri, E., Pattanapanyasat, K., Fucharoen, S., Piknova, B., Schechter, A. N., & Sibmooh, N.
Affiliations
  • Mahidol University (TH)
  • Siriraj Hospital (TH)
  • National Institutes of Health (US)
Corresponding author
Sibmooh, Nathawut
Venue
PLoS ONE
Published
2012-01-20
Volume
7
Issue
1
Pages
e30380
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2017470603
Cited by
109
References
34
Citations by year
2026: 1 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 15 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 9 · 2012: 5
FWCI
7.68
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Mahidol University
  • Thailand Research Fund
  • National Institutes of Health
  • Office of the Higher Education Commission
Topics
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
nitrite, platelet aggregation, erythrocytes, deoxygenation, nitric oxide, hypoxia, ATP release, P-selectin, cyclic GMP, ADP-induced aggregation, whole blood, platelet function
MeSH terms
Adult, Blood Platelets, Cells, Cultured, Erythrocytes, Female, Flow Cytometry, Humans, Male, Nitrites, Oxygen, Platelet Aggregation, Platelet Activation, Young Adult

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