Fergus A, Lee K S
Department of Neurological Surgery, University of Virginia, Charlottesville 22908, USA.
J Cereb Blood Flow Metab. 1997 Sep;17(9):992-1003. doi: 10.1097/00004647-199709000-00009.
The role of GABA in regulating cerebral microvessels was examined in the parenchyma of the hippocampus and the surface of the neocortex. Microvessels were monitored in in vitro slices using computer-assisted videomicroscopy, and synaptically evoked field responses were simultaneously recorded. gamma-Aminobutyric acid (GABA) and the GABAA receptor agonist, muscimol, elicited vasodilation in hippocampal microvessels, whereas the GABAB receptor agonist, baclofen, elicited constriction. The muscimol-induced dilation persisted in the presence of the nitric oxide synthase inhibitor, N-nitro-L-arginine, indicating that this response is not mediated by nitric oxide. Inhibition of neuronal discharge activity with tetrodotoxin did not alter this dilation, but it fully blocked the constrictor response to baclofen. These data suggest that GABAB-mediated, but not GABAA-mediated, responses are dependent on action potential generation. The GABAA receptor antagonists, bicuculline and picrotoxin, elicited constriction, suggesting a tonic dilatory influence by endogenous GABA. Bicuculline-induced constriction was not attenuated by tetrodotoxin. In contrast, these vessels were unresponsive to the GABAB receptor antagonist, 2-hydroxysaclofen. Hippocampal microvessels dilated in response to moderate hypoxia, and this response persisted in the presence of bicuculline, indicating that the hypoxia-induced dilation is not mediated by an action at GABAA receptors. In arterioles located on the surface of the neocortex (i.e., not embedded in the parenchyma of the brain), muscimol elicited vasodilation, whereas bicuculline was ineffective. These results suggest that although these vessels are responsive to GABA, the local concentration of endogenous GABA is insufficient to elicit a tonic effect at rest. These findings raise the possibility that GABA plays a role in local neurovascular signaling in the parenchyma of the brain.
在海马体实质和新皮质表面研究了γ-氨基丁酸（GABA）在调节脑微血管方面的作用。使用计算机辅助视频显微镜在体外切片中监测微血管，并同时记录突触诱发的场反应。γ-氨基丁酸（GABA）和GABAA受体激动剂蝇蕈醇可引起海马微血管舒张，而GABAB受体激动剂巴氯芬则引起收缩。在一氧化氮合酶抑制剂N-硝基-L-精氨酸存在的情况下，蝇蕈醇诱导的舒张持续存在，表明该反应不是由一氧化氮介导的。用河豚毒素抑制神经元放电活动不会改变这种舒张，但它完全阻断了对巴氯芬的收缩反应。这些数据表明，GABAB介导而非GABAA介导的反应依赖于动作电位的产生。GABAA受体拮抗剂荷包牡丹碱和印防己毒素可引起收缩，提示内源性GABA具有紧张性舒张作用。河豚毒素不会减弱荷包牡丹碱诱导的收缩。相反，这些血管对GABAB受体拮抗剂2-羟基-saclofen无反应。海马微血管对中度缺氧有舒张反应，且在荷包牡丹碱存在的情况下该反应持续存在，表明缺氧诱导的舒张不是由GABAA受体作用介导的。在新皮质表面的小动脉（即未嵌入脑实质）中，蝇蕈醇可引起血管舒张，而荷包牡丹碱则无效。这些结果表明，尽管这些血管对GABA有反应，但内源性GABA的局部浓度不足以在静息时产生紧张性作用。这些发现增加了GABA在脑实质局部神经血管信号传导中起作用的可能性。
