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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulation of nitric oxide consumption by hypoxic red blood cells.
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Regulation of nitric oxide consumption by hypoxic red blood cells.

机译:缺氧红细胞对一氧化氮消耗的调节。

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摘要

The homeostasis of nitric oxide (NO) is attained through a balance between its production and consumption. Shifts in NO bioavailability have been linked to a variety of diseases. Although the regulation of NO production has been well documented, its consumption is largely thought to be unregulated. Here, we have demonstrated that under hypoxic conditions, NO accelerates its own consumption by increasing its entry into RBCs. When RBCs were exposed to NO (1:400 NO/heme ratio) under hypoxic conditions to form HbFe(II)NO, the consumption rate of NO increased significantly. This increase in NO consumption converted the bioactivity of serotonin from a vasodilator to a vasoconstrictor in isolated coronary arterioles. We identified HbFe(II)NO as a potential mediator of accelerated NO consumption. Accelerated NO consumption by HbFe(II)NO-bearing RBCs may contribute to hypoxic pulmonary vasoconstriction and the rebound effect seen on termination of NO inhalation therapy. Furthermore, accelerated NO consumption may exacerbate ischemia-mediated vasospasm and nitrate tolerance. Finally, this phenomenon may be an evolved mechanism to stabilize the vasculature in sepsis.
机译:一氧化氮(NO)的稳态通过其生产与消耗之间的平衡来实现。 NO生物利用度的变化与多种疾病有关。尽管已经对NO生产的法规进行了详细记录,但在很大程度上仍认为NO的消耗不受监管。在这里,我们证明了在缺氧条件下,NO通过增加其进入RBC的速度来加速自身的消费。当红细胞在缺氧条件下暴露于NO(1:400 NO /血红素比)时形成HbFe(II)NO,NO的消耗率显着增加。 NO消耗量的增加将5-羟色胺的生物活性从孤立的冠状小动脉中的血管扩张药转变为血管收缩药。我们确定HbFe(II)NO是加速NO消耗的潜在介质。含HbFe(II)NO的RBC加速NO的消耗可能会导致缺氧性肺血管收缩和终止NO吸入治疗时出现的反弹作用。此外,NO消耗的加速可能加剧缺血介导的血管痉挛和硝酸盐耐受性。最后,这种现象可能是稳定败血症中脉管系统的进化机制。

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