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Analysis of the role of NO in cardiovascular disease by use of transgenic mice overexpressing endothelial NO synthase.

利用过表达内皮NO合酶的转基因小鼠分析NO在心血管疾病中的作用。

基本信息

批准号：
10470165
负责人：
YOKOYAMA Mitsuhiro
金额：
$ 2.3万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470165/
关键词：
nitric oxide eNOS transgenic mice vascular response septic shock vascular remodeling adhesion molecule 一酸化窒素血管反応性

项目摘要

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.

我们培育了主要在血管内皮细胞过度表达内皮型一氧化氮合酶（eNOS）的转基因小鼠。使用这种转基因小鼠（eNOS-Tg），我们研究了内源性内皮源性NO在调节血管功能中的作用。1）在eNOS-Tg中，与野生型小鼠相比，血压降低了约20mmHg。因此，内皮源性 NO 可以调节体内血压。2）我们使用主动脉环带进行等长张力测量。来自 eNOS-Tg 的血管表现出对 NO/cGMP 介导的血管舒张剂减弱的血管舒张反应。其机制与血管内可溶性鸟苷酸环化酶活性降低和cGMP依赖性蛋白激酶表达降低有关。3)eNOS-Tg对脂多糖(LPS)诱导的感染性休克具有抵抗力。 LPS 后 eNOS-Tg 的肺损伤减轻，血压降低减弱。血管舒张阻力的降低是eNOS-Tg对LPS诱导的休克具有抵抗力的原因。4)在颈总动脉结扎诱导的血管重塑模型中，eNOS-Tg小鼠的血管重塑程度减弱。结扎后炎症细胞浸润的减弱与粘附分子表达的减少有关，可能与该机制有关。