Co-Investigator(Kenkyū-buntansha) |
KATSUBE Yasuhiro Nippon Medical School, School of Medicine, Associate Professor, 医学部, 助教授 (20246523)
FUKAZAWA Ryuji Nippon Medical School, School of Medicine, Assistant Professor, 医学部, 講師 (80277566)
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Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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Research Abstract |
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.
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