缺氧红细胞对一氧化氮消耗的调节。
Regulation of nitric oxide consumption by hypoxic red blood cells.
作者信息
Han Tae H, Qamirani Erion, Nelson Allyson G, Hyduke Daniel R, Chaudhuri Gautam, Kuo Lih, Liao James C
机构信息
Department of Chemical Engineering, University of California-Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12504-9. doi: 10.1073/pnas.2133409100. Epub 2003 Oct 1.
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.
一氧化氮（NO）的稳态是通过其生成与消耗之间的平衡来实现的。NO生物利用度的改变与多种疾病有关。尽管NO生成的调节已有充分记录，但其消耗在很大程度上被认为是不受调控的。在此，我们证明在低氧条件下，NO通过增加进入红细胞来加速自身的消耗。当红细胞在低氧条件下暴露于NO（NO/血红素比例为1:400）以形成HbFe(II)NO时，NO的消耗速率显著增加。NO消耗的这种增加将血清素在离体冠状动脉小动脉中的生物活性从血管舒张剂转变为血管收缩剂。我们确定HbFe(II)NO是加速NO消耗的潜在介质。携带HbFe(II)NO的红细胞加速NO消耗可能导致低氧性肺血管收缩以及NO吸入治疗终止时出现的反跳效应。此外，加速的NO消耗可能会加剧缺血介导的血管痉挛和硝酸盐耐受性。最后，这种现象可能是一种在脓毒症中稳定血管系统的进化机制。
Zotero 插件