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

交感神经末梢对去甲肾上腺素（NE）的摄取对交感神经裂隙内NE浓度的调节起重要作用。本研究观察了几种实验性高血压大鼠模型的NE摄取和NE溢出情况，发现自发性高血压大鼠（SHR）在肠系膜动脉制备中，交感神经末梢的NE摄取和NE溢出增加。相反，NE摄取和溢出减少成年SHR。Dahl盐敏感大鼠NE溢出增加，但NE摄取减少。在DOCA盐高血压大鼠中，NE摄取减少。提示NE摄取随增龄而改变，在盐依赖性高血压的发生发展中起重要作用。NE溢出和NE摄取突触体部分增加，在年轻的自发性高血压大鼠和成年大鼠减少。中枢交感神经系统的交感神经功能与外周交感神经系统的交感神经功能具有相似的变化趋势，有研究表明体液因素可影响交感神经末梢对NE的摄取。本研究从肾性高血压大鼠尿中部分纯化Na，K^+-ATP酶抑制剂，并观察其对大鼠下丘脑突触体NE摄取的影响。收集肾性高血压患者的尿液，通过凝胶过滤和反相HPLC分离内源性Na，K-ATP酶抑制剂，其显示地高辛样免疫反应性。该物质的极性与地高辛相似，分子量约为400。部分纯化的Na，K+-ATP酶抑制剂可剂量依赖性地抑制大鼠突触体部分对NE的摄取。这些结果表明，内源性Na，K^+-ATP酶抑制剂具有与地高辛相似的化学性质，并对周围神经末梢NE摄取有抑制作用。

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.