Volume 35, Issue. 1, February, 2019

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

Xiao-Jing Yu1 • Yu-Wang Miao1,3 • Hong-Bao Li1 • Qing Su1 • Kai-Li Liu1 • Li-Yan Fu1 • Yi-Kang Hou4 • Xiao-Lian Shi5 • Ying Li1 • Jian-Jun Mu6 • Wen-Sheng Chen7 • Wei Cui8 • Guo-Qing Zhu9 • Philip J. Ebenezer2 • Joseph Francis2,* • Yu-Ming Kang1,*

1Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an, China
2Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, USA
3Genetic Engineering Laboratory, College of Biotechnology, Xi’an University, Xi’an, China
4Department of Plastic and Cosmetic Surgery, Gansu Provincial Hospital, Lanzhou, China
5Department of Pharmacology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
6Department of Cardiovascular Medicine, First Affiliated Hospital of the Medical College of Xi’an Jiaotong University, Xi’an, China
7Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
8Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University Health Science Center, Xi’an, China
9Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China


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 gp91phox expression 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.



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