Molecular biological studies on regulatory systems of the circulation in angiotensinogen gene knockout mice.

为了阐明肾素血管紧张素系统（RAS）在循环系统调节中的作用，使用血管紧张素原基因敲除小鼠（Atg D1-D1/D2-D2）及其对照小鼠（Atg D1/D2 D2）进行体内和体外研究。（1）评估Atg中的激素和电化学变化（2）在Atg的肾脏中，我们发现肾血管特异性变化，例如增生和/或血管平滑肌细胞肥大，肾血管内膜和中膜多层弹性重复，含肾素细胞增多，提示RAS在肾脏正常分化和发育中发挥重要作用。(3)Ang小鼠致密斑中神经元型一氧化氮合酶(N-NOS)受盐摄入量上调和逆向调节，这种酶活性与肾脏肾素产生功能相关。(4)Atg II中D1-D1/D2-D2 小鼠中，缺乏 Ang II 可能通过 Atg D1-D1/D2-D2 小鼠中的翻译和/或翻译后机制上调 ATD21D2-R。(5) 对 Atg D1/D2 D2 心肌细胞中拉伸诱导的 MAP 激酶激活的研究表明，心脏 RAS 的重要性，尽管 Ang II 对于 Atg 中机械拉伸诱导的 MAP 激酶激活并非必不可少。 D1-D1/D2-D2 心肌细胞。此外，我们发现细胞因子 gp 130 可能在心肌细胞中独立于 Ang II 的拉伸诱导的 MAP 激酶激活中发挥作用。

To clarify the role of renin angiotensin system (RAS) in the regulation of circulating system, in vivo and in vitro studies were performed using angiotensinogen gene knockout mice (Atg ィイD1-ィエD1/ィイD2-ィエD2 ) and it's control mice (Atg ィイD1+ィエD1/ィイD2+ィエD2 ).(1) Hormonal and electrochemical changes, evalated in the Atg ィイD1+ィエD1/ィイD2+ィエD2 and Atg ィイD1-ィエD1/ィイD2-ィエD2 mice fed salt restricted or salt loading diets as well as normal salt diet, suggested the essential role of RAS in the blood pressure maintenance as well as water electrolyte homeostasis.(2) In the kidney of Atg ィイD1-ィエD1/ィイD2-ィエD2, we found renal vessel specific changes, such as hyperplasia and/or hypertrophy of vascular smooth muscle cells, multi-layered elastic reduplication in the intima and media of renal vessels, and increasing renin containing cells, suggesting the important role of RAS in the normal differentiation and development of the kidney.(3) Neuronal type of nitric oxide synthase (N-NOS) in the macula densa of Ang ィイD1-ィエD1/ィイD2-ィエD2 mice is upregulated and inversely regulated by salt intake and this enzyme activity is functionally linked to renal renin production.(4) In Atg ィイD1-ィエD1/ィイD2-ィエD2 mice, lack of Ang II may upregulated ATィイD21ィエD2-R through translational and/or posttranslational mechanisms in Atg ィイD1-ィエD1/ィイD2-ィエD2 mice.(5) Studies on stretch-induced MAP kinase activation in Atg ィイD1+ィエD1/ィイD2+ィエD2 cardiac myocytes suggested the importance of cardiac RAS, although Ang II is not indispensable for mechanical stretch-induced activation of MAP kinases in Atg ィイD1-ィエD1/ィイD2-ィエD2 cardiac myocytes. Furthermore we found that cytokine gp 130 may play a role in the stretch-induced MAP kinase activation independently of Ang II in cardiac myocyte.