| Project/Area Number |
10470165
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University, School of Medicine, Professor, 医学部, 教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
EMOTO Noriaki Kobe University, School of Medicine, Assistant Professor, 医学部, 助手 (30294218)
KAWASHIMA Seinosuke Kobe University, Kobe University Hospital, Lecturer, 医学部・附属病院, 講師 (10177678)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | nitric oxide / eNOS / transgenic mice / vascular response / septic shock / vascular remodeling / adhesion molecule / 一酸化窒素 / 血管反応性 |
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| Research Abstract |
We generated trasgenic mice overexpressing endothelial type nitric oxide synthase (eNOS) mainly in the endothelium of vessels. Using this transgenic mice (eNOS-Tg), we investigated the role of endogenous endothelium-derived NO in regulation of vascular function.
1)In eNOS-Tg, blood pressure was decreased by approximately 20 mmHg compared with wild type mice. Thus, endothelium-derived NO serves to regulate blood pressure in vivo.
2)We performed isometric tension measurements using aortic ring strips. Vessels from eNOS-Tg exhibited the attenuated vasodilatory responses to NO/cGMP mediated vasodilators. The mechanisms are related to both reduced activity of soluble guanylate cyclase and decreased expression of cGMP-dependent protein kinase in vessels.
3)eNOS-Tg was resistant to lipopolysaccharide (LPS)-induced septic shock. There were reduced lung injury and attenuated reduction of blood pressure after LPS in eNOS-Tg. The reduced vasodilation of resistance responsible for the resistance of eNOS-Tg to LPS-induced shock.
4)In the vascular remodeling model induced by common carotid artery ligation, the extent of remodeling was attenuated in eNOS-Tg mice. The attenuation of inflammatory cell infiltration after ligation, which was asocated with reduced expression of adhesion molecules, was likely involved in the mechanisms.
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