Norepinephrine Uptake in Nerve Terminals in Hypertension-Effects of Humoral Factor and Sympathetic Activation on Norepinephrine Uptake-

高血压神经末梢去甲肾上腺素的摄取-体液因子和交感神经激活对去甲肾上腺素摄取的影响-

基本信息

批准号：
02670406
负责人：
HANO Takuzo
金额：
$ 1.34万
依托单位：
Wakayama Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

Norepinephrine (NE) uptake in sympathetic nerve terminals plays an important role to regulate the concentration of NE in the sympathetic nerve cleft. In the present study, we examined the NE uptake and NE overflow in the several experimental hypertension models in rats.Young spontaneously hypertensive rats (SHR) showed the increased NE uptake and overflow from the sympathetic nerve terminals in mesenteric arterial preparation. In contrast, NE uptake and overflow were reduced in adult SHR. NE overflow was increased but NE uptake was reduced in Dahl-salt sensitive rats. In DOCA-salt hypertensive rats, NE uptake was reduced. These results suggested that NE uptake is changed by aging and play an important role in the development of hypertension in salt-dependent hypertension. NE overflow and NE uptake in synaptosomal fraction were increased in young spontaneously hypertensive rats and were reduced in adult rats. Sympathetic function in the central nervous system showed a similar trend as that in peripheral sympathetic nervous system.It has been reported that humoral factors can effect the NE uptake in the sympathetic nerve terminals. In the present study, we partially purifies Na, K^+-ATPase inhibitor from the urine of reduced renal mass hypertension and examine the effects of indigenous Na, K^+-ATPase inhibitor on NE uptake in synaptosomal fraction of hypothalamus in rats. Urine of reduced renal mass hypertension was collected and endogenous Na, K-ATPase inhibitor was separated by gel- filtration and reversed HPLC which showed digoxine-like immunoreactivity. The polarity of this substance was similar to digoxine and its molecular weight was about 400. Partially purified Na, K+-ATPase inhibitor suplressed the NE uptake in the synaptosomal fraction in dose-dependent manner in rats. These results showed that endogenous Na, K^+-ATPase inhibitor has a similar chemical characters as digoxine and a inhibitory action on NE uptake in the peripheral nerve endings.

交感神经末端中的去甲肾上腺素（NE）摄取起着调节NE在交感神经裂隙中NE浓度的重要作用。在本研究中，我们检查了大鼠的几种实验性高血压模型中的NE摄取和NE溢流。Young自发性高血压大鼠（SHR）表明，在肠系膜动脉制备中，NE的NE摄取和溢出增加了。相比之下，成人SHR中的NE摄取和溢出降低。 NE溢出增加了，但在Dahl-Salt敏感大鼠中降低了NE摄取。在Doca-Salt高血压大鼠中，NE摄取减少。这些结果表明，NE摄取因衰老而改变，并在盐依赖性高血压中的高血压发展中起重要作用。自发性高血压大鼠的年轻大鼠中，突触体级分的NE溢出和NE摄取增加，并减少成年大鼠。中枢神经系统中的交感神经功能显示出与周围交感神经系统中的类似趋势。据报道，体液因素可以影响交感神经末端的NE摄取。在本研究中，我们从减少肾脏质量高血压的尿液中部分净化Na，K^+ATPase抑制剂，并检查土著Na，K^+ATPase抑制剂对大鼠下丘脑突触体分数中NE摄取的作用。收集肾脏高压降低的尿液，并通过凝胶过滤分离内源性Na，K-ATPase抑制剂，并反转HPLC，该HPLC表现出类似地高毒素样免疫反应性。该物质的极性类似于地高毒素，其分子量约为400。部分纯化的Na，K+-ATPase抑制剂在大鼠中以剂量依赖性的方式将NE的NE摄取。这些结果表明，内源性Na，K^+ATPase抑制剂具有与高毒素相似的化学特征，并且对周围神经末端的NE摄取作用具有类似的化学特征。