Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Br J Anaesth. 2012 Jan;108(1):21-9. doi: 10.1093/bja/aer368. Epub 2011 Nov 14.
It remains unclear whether N-methyl-D-aspartate (NMDA) receptors contribute to cerebral parenchymal vasodilatation, and any effects of clinically used anaesthetics on the dilatation. The present study was designed to examine whether NMDA induces neuronal nitric oxide synthase (NOS)-mediated dilatation, in the cerebral parenchymal arterioles, and whether propofol and superoxide modulate the dilatation in relation to the NMDA receptor activation.
The cerebral parenchymal arterioles within rat brain slices were monitored by a computer-assisted microscopy, and the vasodilatation in response to NMDA (10(-7) to 10(-5) M) was evaluated. Immunofluorescence analysis to neuronal and endothelial NOS and measurement of levels of superoxide and nitric oxide within the arteriole were simultaneously performed.
Propofol, an NMDA receptor antagonist MK801, and a neuronal NOS antagonist S-methyl-l-thiocitrulline (SMTC) reduced NMDA-induced dilation, whereas a superoxide inhibitor, Tiron, and NADPH oxidase inhibitor, gp91ds-tat, augmented NMDA-induced dilatation. Immunofluorescence analysis revealed distribution of neuronal NOS in both endothelial and smooth muscle cells in addition to neuronal cells. NMDA-induced superoxide and nitric oxide within the parenchymal arterioles. The increased superoxide within the arteriole was similarly inhibited by MK801, SMTC, gp91ds-tat, propofol, and a neuronal NOS antagonist vinyl-l-NIO, whereas the level of nitric oxide was reduced by MK801, SMTC, propofol, and vinyl-l-NIO, and it was augmented by gp91ds-tat.
NMDA dilates cerebral parenchymal arterioles possibly via neuronal NOS activation, whereas it produces superoxide via NADPH oxidase. In these arterioles, propofol reduces both the dilatation and superoxide production in response to NMDA.
目前尚不清楚 N-甲基-D-天冬氨酸（NMDA）受体是否参与脑实质血管扩张，以及临床使用的麻醉剂对扩张的影响。本研究旨在研究 NMDA 是否诱导脑实质小动脉中神经元型一氧化氮合酶（NOS）介导的扩张，以及丙泊酚和超氧阴离子是否与 NMDA 受体激活有关调节扩张。
通过计算机辅助显微镜监测大鼠脑片内的脑实质小动脉，并评估 NMDA（10(-7) 至 10(-5) M）引起的血管舒张。同时进行神经元和内皮型 NOS 的免疫荧光分析，并测量小动脉内超氧阴离子和一氧化氮的水平。
丙泊酚、NMDA 受体拮抗剂 MK801 和神经元 NOS 拮抗剂 S-甲基-L-硫代瓜氨酸（SMTC）均降低 NMDA 诱导的舒张，而超氧阴离子抑制剂 Tiron 和 NADPH 氧化酶抑制剂 gp91ds-tat 则增强 NMDA 诱导的舒张。免疫荧光分析显示神经元型 NOS 分布于内皮细胞和血管平滑肌细胞以及神经元细胞中。NMDA 在脑实质小动脉中诱导超氧阴离子和一氧化氮。MK801、SMTC、gp91ds-tat、丙泊酚和神经元 NOS 拮抗剂 vinyl-l-NIO 同样抑制小动脉内 NMDA 诱导的超氧阴离子，而 MK801、SMTC、丙泊酚和 vinyl-l-NIO 降低一氧化氮水平，gp91ds-tat 则增加一氧化氮水平。
NMDA 通过神经元型 NOS 激活扩张脑实质小动脉，而通过 NADPH 氧化酶产生超氧阴离子。在这些小动脉中，丙泊酚降低 NMDA 反应引起的扩张和超氧阴离子产生。
