Efficacy to vascular tonus and vascular remodeling by sympathetic innervation and denervation

交感神经支配和去神经支配对血管紧张和血管重塑的功效

• 批准号: 16591060
• 负责人: OGAWA Shunichi
• 金额: $ 2.18万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591060/
• 关键词: vascular smooth muscle cell; vascular endothelial cell; vascular tonus; vascular remodeling; sympathetic nerve; 血管トーヌス; 交感神経節; 共同培養; バッチクランプ法; L-type Caチャンネル

Main mediators for stress reply to vascular wall are an extra-cellular matrix, vascular growth factors, cytokines, endothelium-derived vascular regulatory factors which are produced and secreted from localized vascular bed. These factors regulate vascular tonus, vascular remodeling (vascular wall-thickness, vascular elasticity, vascular wall weakness), antithrombosis. By the present, many reports are made about vascular tonus, control of vascular remodeling, but there is not the report that examined direct participation to this system of a sympathetic nerve. Therefore we tried to make a co-culture with a sympathetic ganglion and a vascular smooth muscle cell (go through adrenergic α1 receptor) or a vascular endothelium (go through adrenergic α2 receptors), and tested to clarify the regulatory mechanism of vascular tonus and vascular remodeling by direct sympathetic innervation and denervation with this system.The micro-electrophysiological examination to an ion channel of a vascular smooth muscular cell membrane innervated by sympathetic nerve was not able to take effect by a technical problem. On the other hand, gene expressions of ICAM-1 and VCAM-1 which are vascular adhesion molecules, angiotensin II and adrenomedullin which are endothelium-derived vascular regulatory factors, and PDGF and TGF-β which are growth factors, were significantly increase in sympathetic innervated vascular endothelium as compared to those in endothelium alone and sympathetic denervated endothelium. It was the result that was approximately similar with load of the norepinephrine which is a sympathetic nerve secretion to endothelium. This study shows that increased expression of these factors in directly sympathetic innervated endothelium may regulate vascular tonus and vascular remodeling.

血管壁应激反应的主要介质是局部血管床产生和分泌的细胞外基质、血管生长因子、细胞因子、内皮源性血管调节因子等。这些因子调节血管紧张性、血管重塑（血管壁厚度、血管弹性、血管壁弱化）、抗血栓形成。到目前为止，关于血管紧张性、控制血管重构的报道很多，但还没有研究交感神经直接参与这一系统的报道。因此，我们尝试将交感神经节和血管平滑肌细胞进行共培养（通过肾上腺素能α1受体）或血管内皮（通过肾上腺素能α2受体），本实验旨在探讨交感神经直接支配和去交感神经支配对血管紧张性和血管重构的调控机制。对由交感神经支配的血管平滑肌细胞膜的离子通道的电生理检查由于技术问题而不能生效。另一方面，在交感神经支配的血管内皮中，作为血管粘附分子的ICAM-1和VCAM-1、作为内皮源性血管调节因子的血管紧张素II和肾上腺髓质素以及作为生长因子的PDGF和TGF-β的基因表达与单独的内皮和交感神经失神经内皮中的基因表达相比显著增加。结果与交感神经分泌的去甲肾上腺素对内皮的负荷大致相似。本研究表明，这些因子在交感神经直接支配的内皮细胞中的表达增加可能调节血管紧张性和血管重塑。