Li Peng, Zhang Feng, Sun Hai-Jian, Zhang Feng, Han Ying
Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
J Am Soc Hypertens. 2015 Nov;9(11):865-77. doi: 10.1016/j.jash.2015.08.005. Epub 2015 Aug 20.
Excessive sympathetic activity propels the pathogenesis and progression of organ damage in hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation in hypertension. Given the important role of the renin-angiotensin (Ang) system in regulating sympathetic outflow and cardiovascular activity, the present study aimed to investigate the roles of Ang-(1-7) in Ang II-induced CSAR and the sympathetic activation responses in the rostral ventrolateral medulla (RVLM) of hypertensive rats. The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension. Responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin were used to evaluate the CSAR in sinoaortic-denervated and cervical-vagotomized rats with anesthesia. Both Ang II and Ang-(1-7) in the RVLM caused greater increases in RSNA and MAP in 2K1C rats than in sham-operated (sham) rats and enhanced CSAR independently. RVLM pretreatment with Ang-(1-7) dose dependently augmented the effects of Ang II on RSNA, MAP, and CSAR in 2K1C rats. Mas receptor antagonist A-779 in the RVLM exhibited more powerful inhibitory effects on RSNA, MAP, and CSAR than the Ang II type 1 (AT1) receptor antagonist losartan. The expression of both the AT1 receptor and Mas receptor proteins in the RVLM increased, but neither the Ang II nor Ang-(1-7) levels in the RVLM changed significantly in the 2K1C rats compared with the sham rats. These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and sympathetic output not only by itself but also through enhancing the effects of Ang II in renovascular hypertensive rats. Both endogenous Ang-(1-7) and Ang II in the RVLM contribute to the enhanced CSAR and sympathetic activation in renovascular hypertension.
过度的交感神经活动推动了高血压中器官损伤的发病机制和进展。增强的心脏交感神经传入反射（CSAR）参与了高血压中的交感神经激活。鉴于肾素 - 血管紧张素（Ang）系统在调节交感神经输出和心血管活动中的重要作用，本研究旨在探讨Ang -（1 - 7）在Ang II诱导的CSAR以及高血压大鼠延髓头端腹外侧区（RVLM）交感神经激活反应中的作用。采用两肾一夹（2K1C）法诱导肾血管性高血压。在麻醉的去窦主动脉神经和颈迷走神经切断的大鼠中，用肾交感神经活动（RSNA）和平均动脉压（MAP）对心外膜应用辣椒素的反应来评估CSAR。与假手术（sham）大鼠相比，RVLM中的Ang II和Ang -（1 - 7）均使2K1C大鼠的RSNA和MAP升高幅度更大，并独立增强CSAR。在2K1C大鼠中，RVLM预先用Ang -（1 - 7）处理可剂量依赖性增强Ang II对RSNA、MAP和CSAR的作用。RVLM中的Mas受体拮抗剂A - 779对RSNA、MAP和CSAR的抑制作用比Ang II 1型（AT1）受体拮抗剂氯沙坦更强。与假手术大鼠相比，2K1C大鼠RVLM中AT1受体和Mas受体蛋白的表达均增加，但RVLM中Ang II和Ang -（1 - 7）的水平均无显著变化。这些结果表明，RVLM中的Ang -（1 - 7）不仅自身增强CSAR和交感神经输出，还通过增强Ang II在肾血管性高血压大鼠中的作用来实现。RVLM中的内源性Ang -（1 - 7）和Ang II均促成了肾血管性高血压中CSAR增强和交感神经激活。
