Brain amiloride-sensitive Phe-Met-Arg-Phe-NH2-gated Na+ channels and Na+-induced sympathoexcitation and hypertension
Brain amiloride-sensitive Phe-Met-Arg-Phe-NH2-gated Na+ channels and Na+-induced sympathoexcitation and hypertension
复制标题
DOI：
10.1161/hy02t2.103004
复制
发表时间：
2002-02-01
期刊：
影响因子：
8.3
通讯作者：
Leenen, FHH
中科院分区：
文献类型：
--
作者：
Huang, BS;Leenen, FHH
饮食和脑脊液（CSF）Na+可通过脑阿米洛利敏感的Phe-Met-Arg-Phe-NH 2（FMRFamide）门控Na+通道（FaNaChs）发挥作用，引起交感神经兴奋和高血压。我们假设FaNaChs通过激活脑“哇巴因”和脑肾素-血管紧张素系统引起交感神经兴奋。在清醒Wistar大鼠，侧脑室（ICV）输注富含Na+（0.3 mol/L）的人工CSF（aCSF）和ICV注射血管紧张素11或哇巴因增加肾交感神经活动（RSNA），血压（BP）和心率（HR）。阿米洛利类似物ICV苯扎米尔不影响基线值，并阻断ICV输注富含Na+的aCSF的反应，但不阻断ICV血管紧张素11或哇巴因。用ICV抗体Fab片段阻断脑“哇巴因”消除了对ICV FMRFamide和富含Na+的aCSF的应答。在清醒的自发性高血压大鼠（SHR）高盐摄入6周，延长ICV，但不是苯扎明静脉输注在10至20微克/小时显着降低RSNA，BP，和HR的剂量相关的方式。这些反应的程度显着较小的SHR定期盐摄入量。这些结果表明，苄唑可阻断的脑FaNaChs是Wistar大鼠ICV富含Na+的aCSF或SHR高盐摄入引起CSF Na+小幅增加的主要机制。Na+通过FaNaChs进入增强似乎激活脑“哇巴因”和脑肾素-血管紧张素系统，从而增加交感神经流出。脑FaNaChs似乎有助于高盐饮食的SHR的高血压恶化，并在很小程度上，以维持高血压的SHR的常规盐饮食。
Dietary and cerebrospinal fluid (CSF) Na+ may act through brain amiloride-sensitive, Phe-Met-Arg-Phe-NH2 (FMRFamide)-gated Na+ channels (FaNaChs) to cause sympathoexcitation and hypertension. We hypothesized that FaNaChs cause sympathoexcitation via the activation of brain "ouabain" and the brain renin-angiotensin system. In conscious Wistar rats, intracerebroventricular (ICV) infusion of Na+-rich (0.3 mol/L) artificial CSF (aCSF) and ICV injection of angiotensin 11 or ouabain increase renal sympathetic nerve activity (RSNA), blood pressure (BP), and heart rate (HR). ICV benzamil, an amiloride analogue, did not affect baseline values and blocked the responses to ICV infusions of Na+-rich aCSF but not ICV angiotensin 11 or ouabain. ICV FMRFamide also increased RSNA, BP, and HR. Blocking brain "ouabain" with ICV antibody Fab fragments abolished the responses to both ICV FMRFamide and Na+-rich aCSF. In conscious spontaneously hypertensive rats (SHR) on a high salt intake for 6 weeks, prolonged ICV but not intravenous infusion of benzamil at 10 to 20 mug/h significantly decreased RSNA, BP, and HR in a dose-related manner. The extent of these responses was significantly smaller in SHR on regular salt intake. These findings suggest that benzamil-blockable brain FaNaChs represent the major mechanism through which a small increase in CSF Na+ by ICV Na+-rich aCSF in Wistar rats or high salt intake in SHR initiates sympathoexcitation and hypertension. Enhanced Na+ entry through FaNaChs appears to activate brain "ouabain" and the brain renin-angiotensin system and, thereby, increases the sympathetic outflow. Brain FaNaChs appear to contribute to the worsening of hypertension in SHR on a high salt diet and, to a small extent, to the maintenance of hypertension in SHR on a regular salt diet.