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Title: Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation
Authors: Sirada Srihirun
Thanaporn Sriwantana
Supeenun Unchern
Dusadee Kittikool
Egarit Noulsri
Kovit Pattanapanyasat
Suthat Fucharoen
Barbora Piknova
Alan N. Schechter
Nathawut Sibmooh
Mahidol University. Institute of Science and Technology for Research and Development. Thalassemia Research Center
Mahidol University. Faculty of Science. Department of Pharmacology
Keywords: Antioxidant activity;Crocodylus siamensis;Hemoglobin;Secondary structure;Open Access article
Issue Date: 2012
Citation: Plos One. Vol.7, No.1 (2012), 1-9
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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