Kubo Takao, Hagiwara Yukihiko
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Brain Res Bull. 2006 Jan 30;68(5):335-40. doi: 10.1016/j.brainresbull.2005.09.004. Epub 2005 Oct 3.
High dietary salt intake activates the brain renin-angiotensin system in spontaneously hypertensive rats (SHR) and Dahl S rats, resulting in sympathetic hyperactivity and hypertension. Increases of sodium concentration in cerebrospinal fluid (CSF) and/or enhanced responses to CSF sodium are considered to be involved in the high dietary salt-induced activation of central nervous system pathways in those rats. Previously we have demonstrated that intracerebroventricular injection of hypertonic saline increases the neural activity of angiotensin II-sensitive neurons trans-synaptically via endogenous angiotensins in the anterior hypothalamic area (AHA) of rats. In the present study, we examined whether the AHA angiotensin II-sensitive neuron response to hypertonic saline would differ in SHR and Dahl S rats from those of their controls. Male 15- to 16-week-old SHR and age-matched Wistar Kyoto rats (WKY), Dahl S rats and Dahl R rats and Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Intracerebroventricular injection of hypertonic saline increased the firing rate of AHA angiotensin II-sensitive neurons. The threshold sodium concentration for the central sodium-induced increase of neural firing was lower in SHR than those of WKY, Dahl S rats, Dahl R rats and Wistar rats. The increase in neural firing induced by hypertonic saline (250 mM) was greater in SHR than those of other four kinds of rats. Similarly, the threshold sodium concentration was lower in Dahl S rats than those of WKY, Dahl R rats and Wistar rats and the increase in neural firing induced by hypertonic saline (250 mM) was greater in Dahl S rats than those of WKY, Dahl R rats and Wistar rats. In SHR, intracerebroventricular injection of the amiloride-sensitive sodium channel blocker benzamil abolished the hypertonic saline (250 mM)-induced increase in neural firing, but the sodium channel blocker itself did not affect the basal firing of these neurons. These findings indicate that central sodium-induced activation of AHA angiotensin II-sensitive neurons is enhanced in SHR and Dahl S rats.
高盐饮食会激活自发性高血压大鼠（SHR）和Dahl S大鼠的脑肾素-血管紧张素系统，导致交感神经过度活跃和高血压。脑脊液（CSF）中钠浓度的升高和/或对CSF钠的反应增强被认为与高盐饮食诱导的这些大鼠中枢神经系统通路的激活有关。此前我们已经证明，脑室内注射高渗盐水可通过大鼠下丘脑前部区域（AHA）中的内源性血管紧张素跨突触增加血管紧张素II敏感神经元的神经活动。在本研究中，我们检查了AHA血管紧张素II敏感神经元对高渗盐水的反应在SHR和Dahl S大鼠中是否与其对照大鼠不同。将15至16周龄的雄性SHR以及年龄匹配的Wistar Kyoto大鼠（WKY）、Dahl S大鼠、Dahl R大鼠和Wistar大鼠麻醉并进行人工通气。从AHA中的单个神经元记录细胞外电位。脑室内注射高渗盐水可增加AHA血管紧张素II敏感神经元的放电频率。SHR中由中枢钠诱导的神经放电增加的阈值钠浓度低于WKY、Dahl S大鼠、Dahl R大鼠和Wistar大鼠。高渗盐水（250 mM）诱导的SHR神经放电增加大于其他四种大鼠。同样，Dahl S大鼠的阈值钠浓度低于WKY、Dahl R大鼠和Wistar大鼠，高渗盐水（250 mM）诱导的Dahl S大鼠神经放电增加大于WKY、Dahl R大鼠和Wistar大鼠。在SHR中，脑室内注射阿米洛利敏感的钠通道阻滞剂苄amil可消除高渗盐水（250 mM）诱导的神经放电增加，但钠通道阻滞剂本身不影响这些神经元的基础放电。这些发现表明，在SHR和Dahl S大鼠中，中枢钠诱导的AHA血管紧张素II敏感神经元的激活增强。
