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

Authors

Xiao-Jing Yu, Department 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, 710061, China.
Yu-Wang Miao, Department 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, 710061, China.
Hong-Bao Li, Department 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, 710061, China.
Qing Su, Department 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, 710061, China.
Kai-Li Liu, Department 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, 710061, China.
Li-Yan Fu, Department 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, 710061, China.
Yi-Kang Hou, Department of Plastic and Cosmetic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, China.
Xiao-Lian Shi, Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
Ying Li, Department 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, 710061, China.
Jian-Jun Mu, Department of Cardiovascular Medicine, First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, 710061, China.
Wen-Sheng Chen, Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Wei Cui, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
Guo-Qing Zhu, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
Philip J. Ebenezer, Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
Joseph Francis, Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA. jfrancis@lsu.edu.
Yu-Ming Kang, Department 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, 710061, China. ykang@mail.xjtu.edu.cn.

Document Type

Article

Publication Date

2-1-2019

Abstract

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 gp91 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.

Publication Source (Journal or Book title)

Neuroscience bulletin

First Page

47

Last Page

56

Recommended Citation

Yu, X., Miao, Y., Li, H., Su, Q., Liu, K., Fu, L., Hou, Y., Shi, X., Li, Y., Mu, J., Chen, W., Cui, W., Zhu, G., Ebenezer, P. J., Francis, J., & Kang, Y. (2019). Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension. Neuroscience bulletin, 35 (1), 47-56. https://doi.org/10.1007/s12264-018-0297-4