Cosby Kenyatta, Partovi Kristine S, Crawford Jack H, Patel Rakesh P, Reiter Christopher D, Martyr Sabrina, Yang Benjamin K, Waclawiw Myron A, Zalos Gloria, Xu Xiuli, Huang Kris T, Shields Howard, Kim-Shapiro Daniel B, Schechter Alan N, Cannon Richard O, Gladwin Mark T
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 7B15 Bethesda, Maryland 20892, USA.
Nat Med. 2003 Dec;9(12):1498-505. doi: 10.1038/nm954. Epub 2003 Nov 2.
Nitrite anions comprise the largest vascular storage pool of nitric oxide (NO), provided that physiological mechanisms exist to reduce nitrite to NO. We evaluated the vasodilator properties and mechanisms for bioactivation of nitrite in the human forearm. Nitrite infusions of 36 and 0.36 micromol/min into the forearm brachial artery resulted in supra- and near-physiologic intravascular nitrite concentrations, respectively, and increased forearm blood flow before and during exercise, with or without NO synthase inhibition. Nitrite infusions were associated with rapid formation of erythrocyte iron-nitrosylated hemoglobin and, to a lesser extent, S-nitroso-hemoglobin. NO-modified hemoglobin formation was inversely proportional to oxyhemoglobin saturation. Vasodilation of rat aortic rings and formation of both NO gas and NO-modified hemoglobin resulted from the nitrite reductase activity of deoxyhemoglobin and deoxygenated erythrocytes. This finding links tissue hypoxia, hemoglobin allostery and nitrite bioactivation. These results suggest that nitrite represents a major bioavailable pool of NO, and describe a new physiological function for hemoglobin as a nitrite reductase, potentially contributing to hypoxic vasodilation.
亚硝酸盐阴离子构成了一氧化氮（NO）最大的血管储存池，前提是存在将亚硝酸盐还原为NO的生理机制。我们评估了人体前臂中亚硝酸盐的血管舒张特性及其生物活化机制。以36和0.36微摩尔/分钟的速率向肱动脉前臂输注亚硝酸盐，分别导致血管内亚硝酸盐浓度超过和接近生理水平，并在运动前和运动期间增加前臂血流量，无论是否存在一氧化氮合酶抑制。输注亚硝酸盐与红细胞铁亚硝基化血红蛋白的快速形成相关，在较小程度上还与S-亚硝基血红蛋白的形成有关。NO修饰的血红蛋白形成与氧合血红蛋白饱和度成反比。脱氧血红蛋白和脱氧红细胞的亚硝酸盐还原酶活性导致大鼠主动脉环舒张以及NO气体和NO修饰的血红蛋白形成。这一发现将组织缺氧、血红蛋白变构和亚硝酸盐生物活化联系起来。这些结果表明亚硝酸盐代表了NO的主要生物可利用池，并描述了血红蛋白作为亚硝酸盐还原酶的一种新的生理功能，可能有助于缺氧性血管舒张。
