Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
Department of Physiology, Shantou University Medical College, Shantou 515041, China.
Toxicol Appl Pharmacol. 2014 Sep 1;279(2):141-9. doi: 10.1016/j.taap.2014.06.004. Epub 2014 Jun 14.
The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10μg/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM.
下丘脑室旁核（PVN）和延髓头端腹外侧区（RVLM）在交感神经活动的产生和维持中起着关键作用。脑内的肾素-血管紧张素系统（RAS）参与高血压的发病机制。本研究旨在确定 PVN 中的血管紧张素转换酶（ACE）抑制剂是否调节细胞因子并减轻 RVLM 中的氧化应激（ROS），以及降低肾血管性高血压大鼠的血压和交感神经活性。通过双肾一夹（2K1C）方法在雄性 Sprague-Dawley 大鼠中诱导肾血管性高血压。肾血管性高血压大鼠通过渗透微型泵接受双侧 PVN 输注 ACE 抑制剂赖诺普利（LSP，10μg/h）或载体 4 周。肾血管性高血压大鼠的平均动脉压（MAP）、肾交感神经活性（RSNA）和血浆促炎细胞因子（PICs）显著升高。肾血管性高血压大鼠的 PVN 中 ACE 水平也较高，而 RVLM 中的白细胞介素-10（IL-10）水平较低。此外，高血压大鼠 RVLM 中的 PICs、趋化因子 MCP-1、NAD（P）H 氧化酶亚基（gp91（phox））和 ROS 水平升高。LSP 治疗 PVN 减轻了肾血管性高血压大鼠的这些变化。我们的研究结果表明，PVN 中 ACE 抑制在肾血管性高血压中的有益作用部分归因于 RVLM 中细胞因子的调节和氧化应激的减轻。
