The research with genetic engineering regarding the circulatory regulation of spinal microvasculature and the effects of anesthetics

脊髓微血管循环调节及麻醉药作用的基因工程研究

• 批准号: 16390458
• 负责人: KINOSHITA Hiroyuki
• 金额: $ 4.03万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390458/
• 关键词: Spinal microarterioles; Nitric oxide; Synthase; Gene knockout mice; Carbon dioxide; 脊髄内動脈; カリウムチャネル

Spinal slices (150 μm thick) were prepared from the rat or mouse spinal cords. Slices were continuously superfused with control solution at the flow rate of 1.5 ml/min, bubbled with 93% O_2 + 7% CO_2 (PCO_2 = 40 mmHg, pH = 7.4, 37℃). An intraparenchymal arteriole (5.0-10.0 μm in internal diameter) was located within the neuronal tissue, and its internal diameter was continuously monitored with the live computerized videomicroscopy. The videomicroscopy equipment consisted of an inverted microscope. The image of a parenchymal arteriole was transmitted to video camera (C6790-81, Olympus, Tokyo, Japan) and displayed on a computer via a media converter (Physio-Tech, Tokyo, Japan). Changes of intraluminal diameter in spinal microvessels were recorded on computer image files and then analyzed using the image software.During contraction to prostaglandin F_<2α> (0.5 μM), hypercapnia (PCO_2 = 50 mmHg produced by 10% CO2) induced dilation of intraparenchymal spinal arterioles. Addition of acetylcholine (0.1 μM) also induced dilation of these arterioles in the spinal slice from normal mice, whereas this concentration of acetylcholine did not induce dilation of arterioles in the slice from neuronal nitric oxide synthase knockout mice. Effects of anesthetics on above vasodilator responses are under investigation.These results suggest that in spinal microarterioles, carbon dioxide play a role as a vasodilator substance and that neuronal nitric oxide synthase contributes to spinal vasodilator responses induced by physiological agents including acetylcholine.

从大鼠或小鼠脊髓制备脊髓切片（150 μm厚）。对照液以1.5ml/min的流速持续灌流，以93%O_2 + 7%CO_2（PCO_2 = 40 mmHg，pH = 7.4，37℃）鼓泡。在神经元组织内定位一条内径为5.0-10.0 μm的脑实质内小动脉，并通过实时计算机视频显微镜连续监测其内径。视频显微镜设备包括倒置显微镜。将实质小动脉的图像传输到摄像机（C6790-81，Olympus，Tokyo，Japan），并通过媒体转换器（Physio-Tech，Tokyo，Japan）显示在计算机上。在前列腺素F_（2α）（0.5 μM）的作用下，高碳酸血症（10%CO_2产生的PCO_2 = 50 mmHg）引起脊髓实质内微动脉扩张，并记录脊髓微血管管腔内径的变化。在正常小鼠的脊髓切片中，加入乙酰胆碱（0.1 μM）也会诱导这些小动脉扩张，而在神经元型一氧化氮合酶敲除小鼠的切片中，该浓度的乙酰胆碱不会诱导小动脉扩张。麻醉药对上述扩血管反应的影响尚在研究中，这些结果提示：在脊髓微动脉中，二氧化碳起着扩血管物质的作用，神经元型一氧化氮合酶参与了包括乙酰胆碱在内的生理性药物引起的脊髓血管扩张反应。

项目成果

Effects of bupivacaine enantiomers and ropivacaine on vasorelaxation mediated by adenosine Triphosphate-sensitive K+ channels in the rat aorta

• DOI: 10.1097/00000542-200407000-00040
• 发表时间: 2004-07-01
• 期刊: ANESTHESIOLOGY
• 影响因子: 8.8
• 作者: Dojo, M;Kinoshita, H;Hatano, Y
• 通讯作者: Hatano, Y

Augmented activity of adenosine triphosphate-sensitive K^+ channels induced by droperidol in the rat aorta.

氟哌利多在大鼠主动脉中诱导的三磷酸腺苷敏感K + 通道的活性增强。

• 发表时间: 2006
• 期刊: Anesth Analg 102
• 作者: Kinoshita H;Dojo M;Nakahata K;Kimoto Y;Kakutani T;Mizumoto K;Hatano Y
• 通讯作者: Hatano Y

Lidocaine impairs vasodilation mediated by adenosine triphosphate-sensitive K^+ channels but not by inward rectifier K^+ channels in parenchymal microvessels of rat cerebral cortex.

利多卡因损害大鼠大脑皮层实质微血管中由三磷酸腺苷敏感K 通道介导的血管舒张，但不损害内向整流K 通道介导的血管舒张。

• 发表时间: 2004
• 期刊: Anesth Analg 99
• 作者: Kinoshita H;Nakahata K;Dojo M;Kimoto Y;Hatano Y
• 通讯作者: Hatano Y

The inhibitory effects of lidocaine and mexiletine on vasorelaxation mediated by adenosine triphosphate-sensitive K^+ channels and the role of kinases in the porcine coronary artery.

利多卡因和美西律对三磷酸腺苷敏感K + 通道介导的血管舒张的抑制作用以及猪冠状动脉中激酶的作用。

• 发表时间: 2005
• 期刊: Anesthesiology 102
• 作者: Kimoto Y;Kinoshita H;Nakahata K;Dojo M;Hatano Y
• 通讯作者: Hatano Y

Vasodilation Mediated by Inward Rectifier K+ Channels in Cerebral Microvessels of Hypertensive and Normotensive Rats

高血压和正常血压大鼠脑微血管内向整流 K 通道介导的血管舒张作用

• DOI: 10.1213/01.ane.0000194303.00844.5e
• 发表时间: 2006
• 期刊: Anesthesia & Analgesia
• 影响因子: 5.7
• 作者: Katsutoshi Nakahata;H. Kinoshita;Y. Tokinaga;Y. Ishida;Y. Kimoto;M. Dojo;K. Mizumoto;K. Ogawa;Y. Hatano
• 通讯作者: Y. Hatano