Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
复制标题
DOI：
10.1038/nm954
复制
发表时间：
2003-12-01
期刊：
影响因子：
82.9
通讯作者：
Gladwin, MT
中科院分区：
文献类型：
--
作者：
Cosby, K;Partovi, KS;Gladwin, MT
亚硝酸根阴离子包括最大的血管存储池的一氧化氮（NO），提供的生理机制存在，以减少亚硝酸盐NO。我们评估了血管扩张剂的特性和机制，亚硝酸盐在人体前臂的生物活化。亚硝酸盐输注36和0.36 mumol/ min到前臂肱动脉分别导致超生理和接近生理的血管内亚硝酸盐浓度，并在运动前和运动期间增加前臂血流量，有或没有NO合酶抑制。亚硝酸盐输注与红细胞铁-亚硝基血红蛋白的快速形成有关，在较小程度上与S-亚硝基血红蛋白的快速形成有关. NO修饰血红蛋白的形成与氧合血红蛋白饱和度成反比。大鼠主动脉环的舒张以及NO气体和NO修饰血红蛋白的形成是由脱氧血红蛋白和脱氧红细胞的亚硝酸还原酶活性引起的。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，亚硝酸盐代表了一个主要的生物可利用池的NO，并描述了一个新的生理功能，血红蛋白作为亚硝酸盐还原酶，可能有助于缺氧血管舒张。
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 mumol/ 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.