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

应激反应血管壁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、内皮衍生的血管调节因子。这些因素调节血管紧张度、血管重塑(血管壁厚、血管弹性、血管壁无力)、抗血栓形成。到目前为止，已经有很多关于血管紧张性、血管重塑控制的报道，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与血管平滑肌细胞(通过肾上腺素能α1受体)或血管内皮细胞(通过肾上腺素能α2受体)共同培养，并利用该系统对交感神经直接支配和去神经支配血管张力和血管重塑的调节机制进行了试验。交感神经支配的血管平滑肌细胞膜离子通道的显微电生理检测因技术问题而无法实现。另一方面，交感神经支配的血管内皮细胞中血管黏附分子ICAM-1、血管细胞间黏附分子-1、血管紧张素Ⅱ和肾上腺髓质素、生长因子PDGF和转化生长因子-β的基因表达显著高于单纯交感神经支配的血管内皮细胞和交感神经支配的血管内皮细胞。这一结果与去甲肾上腺素的负荷相似，去甲肾上腺素是一种交感神经分泌到内皮的物质。本研究表明，这些因子在直接交感神经支配的内皮细胞中表达增加，可能调节血管紧张性和血管重塑。

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.