Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans
Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans
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DOI：
10.1073/pnas.97.21.11482
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发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Cannon, RO
中科院分区：
文献类型：
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作者：
Gladwin, MT;Shelhamer, JH;Cannon, RO
为了确定内皮源性一氧化氮（NO）与血管内一氧化氮物种在人体血流调节中的相对贡献，我们同时测量了前臂血流量和动脉和静脉血浆亚硝酸盐，低分子量-亚硝酸盐和高分子量-亚硝酸盐，和红细胞S-亚硝基血红蛋白（SNO-Hb）的水平。测量在休息和区域抑制NO合成，然后前臂运动。令人惊讶的是，我们发现显着的循环动脉-静脉血浆亚硝酸盐梯度，提供了一种新的血管内NO的输送源。进一步支持循环亚硝酸盐是生物活性的概念，亚硝酸盐的消耗量显着增加，在抑制区域内皮细胞合成NO的运动。循环S-亚硝基硫醇和SNO-Hb的基础血管张力的调节作用是不太确定的。我们发现，低分子量的S-亚硝基硫醇是检测不到的，S-亚硝基白蛋白水平比以前报道的低两个对数。事实上，S-亚硝基-白蛋白主要在静脉循环中形成，即使在NO合酶抑制期间。然而，SNO-Hb在人体循环中是可测量的（全血中的肱动脉水平为170 nM），动脉-静脉梯度不显著，并且来自SNO-Hb的NO递送是最小的。总之，我们目前的数据表明：（i）循环亚硝酸盐是生物活性的，并提供了血管内NO的输送梯度，（ii）S-亚硝基白蛋白不提供NO从肺部到组织，但在外周循环中形成，和（iii）SNO-Hb和5-亚硝基硫醇发挥最小的作用，在基础血管张力的调节，即使在运动应激。
To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm blood flow and arterial and venous levels of plasma nitrite, LMW-SNOs and HMW-SNOs, and red cell S-nitrosohemoglobin (SNO-Hb). Measurements were made at rest and during regional inhibition of NO synthesis, followed by forearm exercise. Surprisingly, we found significant circulating arterial-venous plasma nitrite gradients, providing a novel delivery source for intravascular NO. Further supporting the notion that circulating nitrite is bioactive, the consumption of nitrite increased significantly with exercise during the inhibition of regional endothelial synthesis of NO. The role of circulating S-nitrosothiols and SNO-Hb in the regulation of basal vascular tone is less certain. We found that low-molecular-weight S-nitrosothiols were undetectable and S-nitroso-albumin levels were two logs lower than previously reported. In fact, S-nitroso-albumin primarily formed in the venous circulation, even during NO synthase inhibition. Whereas SNO-Hb was measurable in the human circulation (brachial artery levels of 170 nM in whole blood), arterial-venous gradients were not significant, and delivery of NO from SNO-Hb was minimal. In conclusion, we present data that suggest (i) circulating nitrite is bioactive and provides a delivery gradient of intravascular NO, (ii) S-nitroso albumin does not deliver NO from the lungs to the tissue but forms in the peripheral circulation, and (iii) SNO-Hb and 5-nitrosothiols play a minimal role in the regulation of basal vascular tone, even during exercise stress.