Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, the Netherlands.
Acta Physiol (Oxf). 2018 Nov;224(3):e13099. doi: 10.1111/apha.13099. Epub 2018 Jun 17.
Conduction of vasomotor responses may contribute to long-term regulation of resistance artery function and structure. Most previous studies have addressed conduction of vasoactivity only during very brief stimulations. We developed a novel set-up that allows the local pharmacological stimulation of arteries in vitro for extended periods of time and studied the conduction of vasomotor responses in rat mesenteric arteries under those conditions.
The new in vitro set-up was based on the pressure myograph. The superfusion chamber was divided halfway along the vessel into two compartments, allowing an independent superfusion of the arterial segment in each compartment. Local and remote cumulative concentration-response curves were obtained for a range of vasoactive agents. Additional experiments were performed with the gap junction inhibitor 18β-glycyrrhetinic acid and in absence of the endothelium.
Phenylephrine-induced constriction and acetylcholine-induced dilation were conducted over a measured distance up to 2.84 mm, and this conduction was maintained for 5 minutes. Conduction of acetylcholine-induced dilation was inhibited by 18β-glycyrrhetinic acid, and conduction of phenylephrine-induced constriction was abolished in absence of the endothelium. Constriction in response to high K was not conducted. Absence of remote stimulation dampened the local response to phenylephrine.
This study demonstrates maintained conduction of vasoactive responses to physiological agonists in rat mesenteric small arteries likely via gap junctions and endothelial cells, providing a possible mechanism for the sustained functional and structural control of arterial networks.
血管舒缩反应的传导可能有助于阻力动脉功能和结构的长期调节。大多数先前的研究仅在非常短暂的刺激期间研究了血管活性的传导。我们开发了一种新的装置,允许在体外长时间局部药理学刺激动脉,并在这些条件下研究大鼠肠系膜动脉中血管舒缩反应的传导。
新的体外装置基于压力肌动描记法。灌流室沿血管的一半分为两个隔室,允许每个隔室中的动脉段独立灌流。获得了一系列血管活性药物的局部和远程累积浓度-反应曲线。还进行了用缝隙连接抑制剂 18β-甘草次酸和没有内皮的附加实验。
在测量的 2.84 毫米距离内进行了去氧肾上腺素诱导的收缩和乙酰胆碱诱导的扩张,并且这种传导可以维持 5 分钟。18β-甘草次酸抑制了乙酰胆碱诱导的扩张的传导,并且在没有内皮的情况下,去氧肾上腺素诱导的收缩的传导被消除。高 K 引起的收缩不能传导。远程刺激的缺失减弱了局部去氧肾上腺素的反应。
这项研究表明,大鼠肠系膜小动脉对生理激动剂的血管活性反应的传导得以维持,可能是通过缝隙连接和内皮细胞,为动脉网络的持续功能和结构控制提供了一种可能的机制。