Blockade of Endogenous Angiotensin-(1–7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension

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 

作者机构：Department of Physiology and PathophysiologyXi’an Jiaotong University School of Basic Medical SciencesKey Laboratory of Environment and Genes Related to DiseasesMinistry of EducationXi’an 710061China Comparative Biomedical SciencesSchool of Veterinary MedicineLouisiana State UniversityBaton RougeLA 70803USA Genetic Engineering LaboratoryCollege of BiotechnologyXi’an UniversityXi’an 710065China Department of Plastic and Cosmetic SurgeryGansu Provincial HospitalLanzhou 730000China Department of PharmacologySchool of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’an 710061China Department of Cardiovascular MedicineFirst Affiliated Hospital of the Medical College of Xi’an Jiaotong UniversityXi’an 710061China Department of Cardiovascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Endocrinology and MetabolismThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an Jiaotong University Health Science CenterXi’an 710061China Key Laboratory of Cardiovascular Disease and Molecular InterventionDepartment of PhysiologyNanjing Medical UniversityNanjing 210029China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2019年第35卷第1期

页      面：47-56页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81600333,81770426,91439120,and 91639105) the China Postdoctoral Science Foundation(2016M602835 and 2016M592802) the Shaanxi Postdoctoral Science Foundation(2016BSHEDZZ91) 

主　　题：High-salt diet Hypertension Angiotensin(1–7) Paraventricular nucleus Pro-inflammatory cytokines 

摘      要：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-1 beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 phoxexpression 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.