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)的摄取对交感神经间隙去甲肾上腺素(NE)浓度的调节具有重要作用。在本研究中，我们研究了几种实验性高血压大鼠模型的NE摄取和NE溢出。幼年自发性高血压大鼠(SHR)在肠系膜动脉准备过程中交感神经末梢的NE摄取和NE溢出增加。相反，成年SHR的NE摄取和溢出减少。Dahl盐敏感大鼠NE外溢增加，NE摄取减少。DOCA-盐性高血压大鼠NE摄取减少。这些结果提示，去甲肾上腺素摄取随年龄增长而改变，在盐依赖型高血压的发生发展中起重要作用。幼年自发性高血压大鼠突触体部分NE外溢和NE摄取增加，成年大鼠则减少。中枢神经系统的交感神经功能与周围交感神经系统的交感神经功能表现出相似的趋势，有报道称体液因素可以影响交感神经末梢的NE摄取。在本研究中，我们从降压性肾性高血压大鼠的尿液中部分纯化了Na，K~+-ATPase抑制剂，并观察了国产Na，K~+-ATPase抑制剂对大鼠下丘脑突触体部去甲肾上腺素摄取的影响。收集肾性高血压患者的尿液，用凝胶过滤和反相高效液相色谱分离内源性Na，K-ATPase抑制物，显示地高辛样免疫反应。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+-ATPase抑制剂以剂量依赖的方式增强大鼠突触体部分对NE的摄取。这些结果表明，内源性Na，K+-ATPase抑制剂具有与地高辛相似的化学特性，并对周围神经末梢的NE摄取具有抑制作用。

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.