Hagiwara Yukihiko, Ohi Masaki, Kubo Takao
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Brain Res Bull. 2005 Oct 15;67(3):203-9. doi: 10.1016/j.brainresbull.2005.06.025.
We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats (SHR). Acetylcholine in the posterior hypothalamic nucleus (PHN) has been implicated in hypertension in SHR. It is suggested that there exist neuronal projections from the PHN to the AHA in rats. In this study, we examined whether cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol, physostigmine and glutamate into the PHN caused an increase in firing rate of AHA angiotensin II-sensitive neurons in anesthetized rats. The carbachol-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was also inhibited by the pressure application of losartan. PHN microinjections of carbachol and glutamate did not affect blood pressure in these anesthetized rats. In conscious rats, PHN microinjection of carbachol produced an increase of blood pressure and the carbachol-induced pressor response was inhibited by bilateral microinjections of losartan into the AHA. These findings indicate that cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by PHN cholinergic stimulation is partly mediated via release of angiotensins at AHA angiotensin II-sensitive neuron levels.
我们之前报道过，大鼠下丘脑前区（AHA）的一些神经元受到内源性血管紧张素的持续激活，并且这些AHA血管紧张素II敏感神经元的活动在自发性高血压大鼠（SHR）中增强。下丘脑后核（PHN）中的乙酰胆碱与SHR的高血压有关。有研究表明，大鼠中存在从PHN到AHA的神经投射。在本研究中，我们检测了PHN中的胆碱能刺激是否会激活AHA血管紧张素II敏感神经元。雄性Wistar大鼠麻醉后进行人工通气。从AHA中的单个神经元记录细胞外电位。向PHN微量注射卡巴胆碱、毒扁豆碱和谷氨酸会导致麻醉大鼠中AHA血管紧张素II敏感神经元的放电频率增加。卡巴胆碱诱导的放电频率增加被向AHA血管紧张素II敏感神经元施加AT1受体拮抗剂氯沙坦所抑制。谷氨酸诱导的放电频率增加也被氯沙坦的压力施加所抑制。向PHN微量注射卡巴胆碱和谷氨酸对这些麻醉大鼠的血压没有影响。在清醒大鼠中，向PHN微量注射卡巴胆碱会导致血压升高，并且卡巴胆碱诱导的升压反应被双侧向AHA微量注射氯沙坦所抑制。这些发现表明，PHN中的胆碱能刺激会激活AHA血管紧张素II敏感神经元。PHN胆碱能刺激诱导的AHA血管紧张素II敏感神经元的激活似乎部分是通过在AHA血管紧张素II敏感神经元水平释放血管紧张素介导的。
