Hu Lian, Zhu Da-Nian, Yu Zhang, Wang John Q, Sun Zhong-Jie, Yao Tai
Department of Physiology, Medical Center of Fudan University (Former Shanghai Medical University), Shanghai 200032, China.
J Appl Physiol (1985). 2002 May;92(5):2153-61. doi: 10.1152/japplphysiol.00261.2001.
In the present study, the changes of amino acids release in the spinal cord after the application of angiotensin II (ANG II) in the rostral ventrolateral medulla (RVLM) and the distribution of ANG receptors on neurons of the RVLM were investigated. A microdialysis experiment showed that microinjection of angiotensin II into the RVLM significantly (P < 0.01) increased the release of aspartate and glutamate in the intermediolateral column of the spinal cord. Immunofluorescence technique combined with confocal microscopy demonstrated that most of the glutamatergic and GABAergic neurons in the RVLM of both Wistar and spontaneously hypertensive rats (SHR) were double labeled with ANG type 1 (AT1) receptor. Immunocytochemical studies demonstrated that the mean optic density of AT1 receptor of the cell surface as well as the whole cell was higher (P < 0.05) in SHR than that in Wistar rats, indicating that the higher expression of AT1 receptors in the RVLM may contribute to the higher responsiveness of SHR to ANG II stimulation. Immunogold staining and electronmicroscopic study demonstrated that AT1 receptor in the RVLM was distributed on the rough endoplasmic reticulum, cell membrane, and nerve processes. The results suggest that effects evoked by ANG II in the RVLM are closely related to glutamatergic and GABAergic pathways. These results indirectly support the hypothesis that ANG II in the RVLM may activate vasomotor sympathetic glutamatergic neurons, leading to an increase in sympathetic nerve activity and arterial blood pressure.
在本研究中,我们调查了在延髓头端腹外侧区(RVLM)应用血管紧张素II(ANG II)后脊髓中氨基酸释放的变化以及ANG受体在RVLM神经元上的分布。微透析实验表明,向RVLM微量注射血管紧张素II可显著(P < 0.01)增加脊髓中间外侧柱中天冬氨酸和谷氨酸的释放。免疫荧光技术结合共聚焦显微镜显示,Wistar大鼠和自发性高血压大鼠(SHR)的RVLM中大多数谷氨酸能和γ-氨基丁酸能神经元都与ANG 1型(AT1)受体呈双重标记。免疫细胞化学研究表明,SHR细胞表面以及整个细胞的AT1受体平均光密度高于Wistar大鼠(P < 0.05),这表明RVLM中AT1受体的高表达可能导致SHR对ANG II刺激的更高反应性。免疫金染色和电子显微镜研究表明,RVLM中的AT1受体分布在粗面内质网、细胞膜和神经突起上。结果表明,ANG II在RVLM中引起的效应与谷氨酸能和γ-氨基丁酸能途径密切相关。这些结果间接支持了这样的假设,即RVLM中的ANG II可能激活血管运动交感谷氨酸能神经元,导致交感神经活动和动脉血压升高。