Clarification of central nervous system mechanism involved in activation of the sympathetic nervous system in heart failure.

1.采用腹主动脉-腔静脉分流术建立大鼠心力衰竭模型。心衰大鼠出现左心室扩大和血流动力学改变，尿儿茶酚胺排泄量和最大肾交感神经活动(SNA)均高于对照组。在孤束核(NTS)内微量注射血管紧张素1(AT1)受体拮抗剂。AT1受体拮抗剂降低心力衰竭大鼠的动脉压和肾SNA的程度大于对照组。心衰大鼠延髓血管紧张素转换酶基因表达明显高于对照组。这些结果表明，NTS中肾素-血管紧张素系统的激活有助于HF2中SNA的增强。将携带内皮型一氧化氮合酶(ENOS)和β-半乳糖苷酶基因的腺病毒载体体内导入NTS。…检测大鼠脑内eNOS蛋白的表达通过体内微透析法测量NTS中亚硝酸盐和硝酸盐的产量增加更多。在基因转移后第5天至第10天，AdeNOS治疗组在清醒状态下使用无线电遥测系统监测的血压和心率显著降低。AdeNOS治疗组在基因转移后第7天尿去甲肾上腺素排泄量也减少。我们的结果表明，eNOS在NTS的过度表达降低了清醒大鼠的血压、心率和SNA。冠脉结扎法建立小鼠心衰模型。超声心动图显示，这些小鼠的左心室扩大，左心室收缩功能降低。此外，这些小鼠24小时的尿去甲肾上腺素排泄量高于对照组小鼠。此外，Western印迹分析显示，与对照组相比，心力衰竭组小鼠神经元一氧化氮合酶的表达降低。我们正在将eNOS基因导入心力衰竭小鼠的脑干。较少

1. Heart failure (HF) was induced by an aortocaval shunt in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of HF.Urinary catecholamine excretion and maximal renal sympathetic nerve activity (SNA) were greater in rats with HF than in the control rats. Microinjection of an angiotensin type 1 (AT1) receptor antagonist into the nucleus tractus solitarius (NTS) was performed. The arterial pressure and renal SNA were reduced by an AT1 receptor antagonist to a greater degree in HF rats than in the control rats. The expression of angiotensin converting enzyme mRNA in the medulla was greater in the HF rats than in the control rats. These results suggest that activation of the renin-angiotensin system in the NTS contributes to an enhanced SNA in HF.2. Adenovirus vectors encoding either endothelial nitric oxide synthase (eNOS)(AdeNOS) or β-galactocidase were transfected into the NTS in vivo. In the AdeNOS-treated rats, the local expression of eNOS protein and by … More increased production of nitrite and nitrate in the NTS measured by in vivo microdialysis. Blood pressure and heart rate, monitored by the use of a radiotelemetry system in a conscious state, were significantly decreased in the AdeNOS-treated group at day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion also was decreased at day 7 after the gene transfer in the AdeNOS-treated group. Our results indicate that overexpression of eNOS in the NTS decreases blood pressure, heart rate, and SNA in conscious rats.3. HF was induced by coronary ligation in the mouse. These mice exhibited a left ventricular dilatation and a reduced left ventricular systolic function by echocardiography. In addition, urinary norepinephrine excretion for 24 hours was greater in these mice than in the control mice. Furthermore, neuronal NOS expression was reduced in the HF mice by Western blot analysis as compared with that in the control mice. We are transfecting eNOS into the brain stem in the HF mice. Less