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Neuroscience Bulletin

, Volume 35, Issue 1, pp 47–56 | Cite as

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

  • 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 FrancisEmail author
  • Yu-Ming KangEmail author
Original Article
  • 225 Downloads

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 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.

Keywords:

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

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81600333, 81770426, 91439120, and 91639105), the China Postdoctoral Science Foundation (2016M602835 and 2016M592802), and the Shaanxi Postdoctoral Science Foundation (2016BSHEDZZ91).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Xiao-Jing Yu
    • 1
  • Yu-Wang Miao
    • 1
    • 3
  • Hong-Bao Li
    • 1
  • Qing Su
    • 1
  • Kai-Li Liu
    • 1
  • Li-Yan Fu
    • 1
  • Yi-Kang Hou
    • 4
  • Xiao-Lian Shi
    • 5
  • Ying Li
    • 1
  • Jian-Jun Mu
    • 6
  • Wen-Sheng Chen
    • 7
  • Wei Cui
    • 8
  • Guo-Qing Zhu
    • 9
  • Philip J. Ebenezer
    • 2
  • Joseph Francis
    • 2
    Email author
  • Yu-Ming Kang
    • 1
    Email author
  1. 1.Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to DiseasesMinistry of EducationXi’anChina
  2. 2.Comparative Biomedical Sciences, School of Veterinary MedicineLouisiana State UniversityBaton RougeUSA
  3. 3.Genetic Engineering Laboratory, College of BiotechnologyXi’an UniversityXi’anChina
  4. 4.Department of Plastic and Cosmetic SurgeryGansu Provincial HospitalLanzhouChina
  5. 5.Department of Pharmacology, School of Basic Medical SciencesXi’an Jiaotong University Health Science CenterXi’anChina
  6. 6.Department of Cardiovascular MedicineFirst Affiliated Hospital of the Medical College of Xi’an Jiaotong UniversityXi’anChina
  7. 7.Department of Cardiovascular SurgeryXijing Hospital, Fourth Military Medical UniversityXi’anChina
  8. 8.Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an Jiaotong University Health Science CenterXi’anChina
  9. 9.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of PhysiologyNanjing Medical UniversityNanjingChina

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