Journal Article

Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function

Park, Ji Won, Noguchi, Constance T., Piknova, Barbora, Schechter, Alan N., Huang, Paul L.

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenosine Triphosphate - metabolism / Agglomeration / Analysis / Analysis of Variance / Animals / Anions / Antibiotics / ATP / Biology / Biomarkers / Biomarkers - blood / Bleeding / Blood / Blood cells / Blood platelets / Blood Platelets - drug effects / Blood Platelets - physiology / Cardiovascular diseases / Control / Deoxygenation / Diabetes / Diet / Dietary restrictions / Dietary Supplements / Drinking water / Endothelium / Erythrocytes / Gene expression / Heart diseases / Hemostasis / Hemostatics / Homeostasis / Hypoxia / Kidney diseases / Luminescent Measurements / Mammals / Medicine / Metabolites / Mice / Mice, Inbred C57BL / Mice, Knockout / Nitrates / Nitrates - blood / Nitrates - pharmacology / Nitric oxide / Nitric Oxide Synthase Type III - genetics / Nitric-oxide synthase / Nitrites / Nitrites - blood / Nitrites - pharmacology / Nitrogen dioxide / Nitrogen oxides / Nutrient deficiency / Platelet aggregation / Platelet Aggregation - drug effects / Platelet Aggregation - physiology / Thromboembolism / Thrombosis