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

我们制备了主要在血管内皮过度表达内皮型一氧化氮合酶（eNOS）的转基因小鼠。利用这种转基因小鼠（eNOS-Tg），我们研究了内源性内皮源性NO在血管功能调节中的作用。1)与野生型小鼠相比，eNOS-Tg使血压降低约20 mmHg。因此，内皮源性NO在体内具有调节血压的作用。2)我们使用主动脉环条进行了等距张力测量。来自eNOS-Tg的血管对NO/cGMP介导的血管舒张剂表现出减弱的血管舒张反应。其机制与血管中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）诱导的脓毒性休克具有抵抗性。LPS治疗eNOS-Tg后肺损伤减轻，血压下降减弱。eNOS-Tg抵抗lps诱导休克的血管舒张性降低。4)在颈总动脉结扎诱导的血管重构模型中，eNOS-Tg小鼠的血管重构程度减弱。结扎后炎性细胞浸润减弱，与粘附分子表达减少有关，可能参与其机制。

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.