Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension.
Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension.
复制标题
阻断下丘脑室旁核中的内源性血管紧张素-(1-7) 可减弱高盐引起的交感兴奋和高血压。
DOI：
10.1007/s12264-018-0297-4
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发表时间：
2019
影响因子：
5.6
通讯作者：
Yu-Ming Kang
中科院分区：
文献类型：
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作者：
Xiao-Jing Yu;Yu-Wang Miao;Hong-Bao Li;Qing Su;Kai-Li Liu;Li-Yan Fu;Yi-Kang Hou;Xiao-Lian Shi;Ying Li;Jian-Jun Mu;Wen-Sheng Chen;Wei Cui;Guo-Qing Zhu;Philip J. Ebenezer;Joseph Francis;Yu-Ming Kang
血管紧张素（Ang）-（1-7）是肾素-血管紧张素系统的重要生物活性肽。本研究旨在确定在盐诱导的高血压中抑制下丘脑室旁核（PVN）中的Ang-（1-7）是否通过调节PVN中的促炎细胞因子（PIC）和氧化应激来减弱交感神经活性并升高血压。大鼠喂食高盐（8%NaCl）或正常盐饮食（0.3%NaCl）10周，然后双侧PVN微量注射Ang-（1-7）拮抗剂A-779或溶媒。我们发现，盐诱导的高血压大鼠的平均动脉压（MAP）、肾交感神经活动（RSNA）和血浆去甲肾上腺素（NE）显著升高。高盐饮食还导致PIC中白细胞介素-6、白细胞介素-1 β、肿瘤坏死因子α和单核细胞趋化蛋白-1水平升高，以及PVN中gp 91 phox表达和超氧化物产生增加。双侧PVN微量注射A-779（3 nmol/50 nL），不仅能降低MAP、RSNA和NE，而且能降低PVN的PIC和氧化应激。这些结果表明，在盐诱导的高血压的MAP和交感神经活性的增加可以通过阻断PVN中的内源性Ang-（1-7），通过调节PIC和氧化应激来抑制。
Angiotensin (Ang)-(1–7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1–7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1–7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91phoxexpression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1–7) in the PVN, through modulation of PICs and oxidative stress.