Yim Peter D, Gallos George, Lee-Kong Steven A, Dan William, Wu Amy D, Xu Dingbang, Berkowitz Dan E, Emala Charles W
Department of Anesthesiology, Columbia University, New York, New York, USA,
Department of Anesthesiology, Columbia University, New York, New York, USA.
J Vasc Res. 2020;57(3):113-125. doi: 10.1159/000505456. Epub 2020 Feb 25.
The clinical administration of GABAergic medications leads to hypotension which has classically been attributed to the modulation of neuronal activity in the central and peripheral nervous systems. However, certain types of peripheral smooth muscle cells have been shown to express GABAA receptors, which modulate smooth muscle tone, by the activation of these chloride channels on smooth muscle cell plasma membranes. Limited prior studies demonstrate that non-human large-caliber capacitance blood vessels mounted on a wire myograph are responsive to GABAA ligands. We questioned whether GABAA receptors are expressed in human resistance arteries and whether they modulate myogenic tone. We demonstrate the novel expression of GABAA subunits on vascular smooth muscle from small-caliber human omental and mouse tail resistance arteries. We show that GABAA receptors modulate both plasma membrane potential and calcium responses in primary cultured cells from human resistance arteries. Lastly, we demonstrate functional physiologic modulation of myogenic tone via GABAA receptor activation in human and mouse arteries. Together, these studies demonstrate a previously unrecognized role for GABAA receptors in the modulation of myogenic tone in mouse and human resistance arteries.
γ-氨基丁酸能药物的临床应用会导致低血压，传统上认为这是由于中枢和外周神经系统中神经元活动的调节所致。然而，已表明某些类型的外周平滑肌细胞表达γ-氨基丁酸A受体，通过激活这些平滑肌细胞质膜上的氯离子通道来调节平滑肌张力。先前有限的研究表明，安装在线肌动描记器上的非人类大口径电容性血管对γ-氨基丁酸A配体有反应。我们质疑γ-氨基丁酸A受体是否在人类阻力动脉中表达，以及它们是否调节肌源性张力。我们证明了γ-氨基丁酸A亚基在小口径人类网膜和小鼠尾部阻力动脉的血管平滑肌上的新表达。我们表明，γ-氨基丁酸A受体调节人类阻力动脉原代培养细胞中的质膜电位和钙反应。最后，我们证明了通过γ-氨基丁酸A受体激活在人类和小鼠动脉中对肌源性张力的功能性生理调节。总之，这些研究证明了γ-氨基丁酸A受体在调节小鼠和人类阻力动脉肌源性张力方面以前未被认识的作用。
