title: Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Sirada
authors.initials: S
authors.lastname: Srihirun
authors.forename: Thanaporn
authors.initials: T
authors.lastname: Sriwantana
authors.forename: Supeenun
authors.initials: S
authors.lastname: Unchern
authors.forename: Dusadee
authors.initials: D
authors.lastname: Kittikool
authors.forename: Egarit
authors.initials: E
authors.lastname: Noulsri
authors.forename: Kovit
authors.initials: K
authors.lastname: Pattanapanyasat
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Barbora
authors.initials: B
authors.lastname: Piknova
authors.forename: Alan N
authors.initials: AN
authors.lastname: Schechter
authors.forename: Nathawut
authors.initials: N
authors.lastname: Sibmooh
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009573:Nitrites / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D055815:Young Adult
chemical_list: D009573:Nitrites; D010100:Oxygen