Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig University Giessen, Rudolph-Buchheimstr. 7, 35392, Giessen, Germany.
Department of Anesthesiology and Intensive Care Medicine, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
Eur J Med Res. 2018 Aug 25;23(1):38. doi: 10.1186/s40001-018-0335-8.
Ischemia of intestinal organs is a main cause of complications in surgical intensive care patients. Changes in the tonus of arteries contributing to vascular resistance play an important role in the determination of blood flow and thus oxygen supply of various abdominal organs. It is generally acknowledged that hypoxia itself is able to alter arterial tonus and thus blood flow.
The present study compared the effects of various degrees of hypoxia on second-order mesenteric arteries from male C57BL/6J mice. After vessel isolation and preparation, we assessed vessel diameter using an arteriograph perfusion chamber. Investigating mechanisms promoting hypoxia-induced vasodilatation, we performed experiments in Ca-containing and Ca-free solutions, and furthermore, Ca-influx was inhibited by NiCl, eNOS-, and TASK1-mice were investigated too.
Mild hypoxia 14.4% O induced, in 50% of mesenteric artery segments from wild-type (wt) mice, a vasodilatation; severe hypoxia recruited further segments responding with vasodilatation reaching 80% under anoxia. However, the extension of dilatation of luminal arterial diameter reduced from 1.96% ± 0.55 at 14.4% O to 0.68% ± 0.13 under anoxia. Arteries exposed to hypoxia in Ca-free solution responded to lower oxygen levels with increasing degree of vasodilatation (0.85% ± 0.19 at 14.4% O vs. 1.53% ± 0.42 at 2.7% O). Inhibition of voltage-gated Ca-influx using NiCl completely diminished hypoxia-induced vasodilatation. Instead, all arterial segments investigated constricted. Furthermore, we did not observe altered hypoxia-induced vasomotion in eNOS- or TASK1 mice compared to wt animals.
The present study demonstrated that hypoxic vasodilatation in mice mesenteric arteries is mediated by a NO-independent mechanism. In this experimental setting, we found evidence for Ca-mediated activation of ion channels causing hypoxic vasodilatation.
肠器官缺血是外科重症监护患者发生并发症的主要原因。参与血管阻力的动脉张力变化在确定各种腹部器官的血流和氧气供应方面起着重要作用。人们普遍认为，缺氧本身能够改变动脉张力，从而改变血流。
本研究比较了不同程度缺氧对雄性 C57BL/6J 小鼠二级肠系膜动脉的影响。在血管分离和准备后，我们使用血管造影灌注室评估血管直径。为了研究促进缺氧诱导血管舒张的机制，我们在含有 Ca 和无 Ca 溶液中进行了实验，此外，还通过 NiCl、eNOS- 和 TASK1 抑制 Ca 内流，研究了 Ca 内流对缺氧诱导血管舒张的影响。
轻度缺氧 14.4% O 诱导 50%的野生型（wt）小鼠肠系膜动脉段发生血管舒张；严重缺氧招募更多的血管段对血管舒张做出反应，在缺氧下达到 80%。然而，管腔动脉直径扩张的扩展从 14.4% O 时的 1.96%±0.55 减少到缺氧时的 0.68%±0.13。在无 Ca 溶液中暴露于缺氧的动脉对较低的氧水平反应程度增加，血管舒张程度增加（14.4% O 时为 0.85%±0.19，2.7% O 时为 1.53%±0.42）。使用 NiCl 抑制电压门控 Ca 内流完全消除了缺氧诱导的血管舒张。相反，所有研究的动脉段都收缩。此外，与 wt 动物相比，我们在 eNOS-或 TASK1 小鼠中没有观察到改变的缺氧诱导血管运动。
本研究表明，小鼠肠系膜动脉的缺氧性血管舒张是由一种非一氧化氮依赖性机制介导的。在这种实验环境下，我们发现了 Ca 介导的离子通道激活导致缺氧性血管舒张的证据。
