Nitric oxide in the human respiratory cycle
Nitric oxide in the human respiratory cycle
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DOI：
10.1038/nm718
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发表时间：
2002-07-01
期刊：
影响因子：
82.9
通讯作者：
Stamler, JS
中科院分区：
文献类型：
--
作者：
McMahon, TJ;Moon, RE;Stamler, JS
一氧化氮（NO）与血红蛋白（Hb）的相互作用可以通过改善人体呼吸循环中缺氧血管舒张和高氧血管收缩的经典生理反应来调节氧（O-2）的吸收和输送。在这里，我们表明，在体外和离体系统以及健康成年人交替暴露于缺氧或高氧（扩张或收缩肺动脉和体动脉在体内），结合NO血红素（FeNO）和巯基（SNO）的血红蛋白变化的功能HbO（2）饱和度（FeO 2）。此外，我们发现，红细胞（RBC）/SNO介导的血管扩张活性在很宽的范围内与FeO 2成反比，而RBC诱导的血管收缩与FeO 2直接相关。因此，天然RBC对氧张力（pO（2））的变化作出反应，具有分级的血管扩张剂和血管收缩剂活性，这模拟了人类对O-2摄取和递送的生理反应。因此，监测和操纵血液中NO水平以及O-2和二氧化碳水平的能力可能在许多人类疾病的诊断和治疗以及新疗法的开发中证明是有用的。我们的研究结果也有助于阐明红细胞恶液质和心血管疾病发病率之间的联系。
Interactions of nitric oxide (NO) with hemoglobin (Hb) could regulate the uptake and delivery of oxygen (O-2) by subserving the classical physiological responses of hypoxic vasodilation and hyperoxic vasconstriction in the human respiratory cycle. Here we show that in in vitro and ex vivo systems as well as healthy adults alternately exposed to hypoxia or hyperoxia (to dilate or constrict pulmonary and systemic arteries in vivo), binding of NO to hemes (FeNO) and thiols (SNO) of Hb varies as a function of HbO(2) saturation (FeO2). Moreover, we show that red blood cell (RBC)/SNO-mediated vasodilator activity is inversely proportional to FeO2 over a wide range, whereas RBC-induced vasoconstriction correlates directly with FeO2. Thus, native RBCs respond to changes in oxygen tension (pO(2)) with graded vasodilator and vasoconstrictor activity, which emulates the human physiological response subserving O-2 uptake and delivery. The ability to monitor and manipulate blood levels of NO, in conjunction with O-2 and carbon dioxide, may therefore prove useful in the diagnosis and treatment of many human conditions and in the development of new therapies. Our results also help elucidate the link between RBC dyscrasias and cardiovascular morbidity.