Erythrocytes are the major intravascular storage sites of nitrite in human blood
Erythrocytes are the major intravascular storage sites of nitrite in human blood
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DOI：
10.1182/blood-2005-02-0567
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发表时间：
2005-07-15
期刊：
影响因子：
20.3
通讯作者：
Schechter, AN
中科院分区：
文献类型：
--
作者：
Dejam, A;Hunter, CJ;Schechter, AN
血浆中亚硝酸根离子水平已被用作体内一氧化氮合酶（NOS）活性的指标。最近的数据表明，亚硝酸盐是一个潜在的血管内储存一氧化氮（NO），生物激活的亚硝酸还原酶活性的脱氧血红蛋白。血液和红细胞中亚硝酸盐的精确水平和区室化尚未确定。全血和红细胞中的亚硝酸盐水平测定使用还原化学发光结合铁氰化物为基础的血红蛋白氧化测定，以防止亚硝酸盐破坏。该方法可在室温下24小时内对全血亚硝酸盐进行灵敏且线性的测量。在15名健康志愿者的血浆、红细胞和全血中测得的亚硝酸盐水平分别为121 ± 9、288 ± 47和176 ± 17 nM，表明红细胞中亚硝酸盐的浓度高得惊人。红细胞中的大多数亚硝酸盐位于不与蛋白质结合的胞质溶胶中。在人类中，我们发现全血和红细胞中亚硝酸盐的动脉-静脉梯度显著。切应力和乙酰胆碱介导的内皮NOS的刺激显着增加静脉亚硝酸盐水平。这些研究表明，动态血管内NO代谢，其中内皮NOS衍生的NO被稳定为亚硝酸盐，通过红细胞运输，并在动脉到静脉运输过程中消耗。
Plasma levels of nitrite ions have been used as an index of nitric oxide synthase (NOS) activity in vivo. Recent data suggest that nitrite is a potential intravascular repository for nitric oxide (NO), bioactivated by a nitrite reductase activity of deoxyhemoglobin. The precise levels and compartmentalization of nitrite within blood and erythrocytes have not been determined. Nitrite levels in whole blood and erythrocytes were determined using reductive chemiluminescence in conjunction with a ferricyanide-based hemoglbin oxidation assay to prevent nitrite destruction. This method yields sensitive and linear measurements of whole blood nitrite over 24 hours at room temperature. Nitrite levels measured in plasma, erythrocytes, and whole blood from 15 healthy volunteers were 121 plus or minus 9, 288 plus or minus 47, and 176 plus or minus 17 nM, indicating a surprisingly high concentration of nitrite within erythrocytes. The majority of nitrite in erythrocytes is located in the cytosol unbound to proteins. In humans, we found a significant artery-to-vein gradient of nitrite in whole blood and erythrocytes. Shear stress and acetylcholine-mediated stimulation of endothelial NOS significantly increased venous nitrite levels. These studies suggest a dynamic intravascular NO metabolism in which endothelial NOS-derived NO is stabilized as nitrite, transported by erythrocytes, and consumed during arterial-to-venous transit.