title: Inhibitory effect of nitrite on coagulation processes demonstrated by thrombelastography.
abstract: Nitric oxide (NO) can be generated by two-step reduction pathway in which nitrate is converted first into nitrite and then into NO via several mechanisms, as well as from arginine by endogenous nitric oxide synthase (NOS). We have recently shown that nitrite ions in the presence of erythrocytes inhibit platelet aggregation and activation, as measured by aggregometry and flow cytometric analysis of P-selectin, through its reduction to NO under partially deoxygenated conditions. In the current study, we investigated how nitrite may affect overall clotting processes via modulating platelet function using thrombelastography (TEG). We measured three major TEG parameters, reaction time (R, time to initial fibrin formation), α angle (velocity of clot growth) and maximum amplitude (MA, maximum clot strength) using blood from healthy volunteers. An NO donor (DEANONOate) showed inhibitory effects on all TEG parameters in platelet rich plasma (PRP) and whole blood, resulting in delayed R, decreased angle, and reduced MA in a dose dependent manner. Nitrite ions also exhibited inhibitory effects in whole blood at 20% hematocrit, and this was greatly enhanced under hypoxic conditions, being demonstrable at 0.1 μM concentration. Neither compound changed any TEG parameters in plasma. Our results suggest that nitrite affects overall blood clotting and that TEG may be used to follow this process. Further the physiological effects of factors which determine NO bioavailability, such as endogenous levels of blood and tissue nitrite, may be useful as biomarkers for predicting hemostatic potential.
authors.affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: B
authors.initials: B
authors.lastname: Piknova
authors.affiliation: Department of Laboratory Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: K
authors.initials: K
authors.lastname: Nghiem
authors.affiliation: Department of Laboratory Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: J N
authors.initials: JN
authors.lastname: Lozier
authors.affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: alans@intra.niddk.nih.gov.
authors.forename: A N
authors.initials: AN
authors.lastname: Schechter
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D064368:Healthy Volunteers; D006801:Humans; D008875:Middle Aged; D009573:Nitrites / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013916:Thrombelastography; D055815:Young Adult
chemical_list: D009573:Nitrites
keywords: Erythrocytes; Hypoxia; Nitric oxide; Nitrites; Platelet; Thrombelastography