Neuroscience Bulletin

, Volume 35, Issue 1, pp 57–66 | Cite as

Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus

  • Xiao-Jing Yu
  • Ya-Nan Zhao
  • Yi-Kang Hou
  • Hong-Bao Li
  • Wen-Jie Xia
  • Hong-Li Gao
  • Kai-Li Liu
  • Qing Su
  • Hui-Yu Yang
  • Bin Liang
  • Wen-Sheng Chen
  • Wei Cui
  • Ying LiEmail author
  • Guo-Qing Zhu
  • Zhi-Ming YangEmail author
  • Yu-Ming KangEmail author
Original Article


Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.


Hypertension Paraventricular nucleus Sympathoexcitation Metformin Oxidative stress 



We gratefully acknowledge Jian-Jun Mu (Department of Cardiology, The First Affiliated Hospital of Xi’an Jiaotong University) for providing the Dahl salt-sensitive rats. This work was supported by the National Natural Science Foundation of China (81600333, 81770426, 81800372, 91439120, and 91639105), the Postdoctoral Science Foundation of China (2016M602835, 2017M620457), and the Postdoctoral Science Foundation of Shaanxi Province, China (2016BSHEDZZ91).

Conflict of interest

The authors declare no competing financial interests.


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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
  • Ya-Nan Zhao
    • 1
    • 3
  • Yi-Kang Hou
    • 6
  • Hong-Bao Li
    • 1
  • Wen-Jie Xia
    • 1
  • Hong-Li Gao
    • 1
  • Kai-Li Liu
    • 1
  • Qing Su
    • 1
  • Hui-Yu Yang
    • 2
  • Bin Liang
    • 2
  • Wen-Sheng Chen
    • 4
  • Wei Cui
    • 5
  • Ying Li
    • 1
    Email author
  • Guo-Qing Zhu
    • 7
  • Zhi-Ming Yang
    • 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, Ministry of Education Key Laboratory of Environment and Genes Related to DiseasesXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of CardiologySecond Affiliated Hospital of Shanxi Medical UniversityTaiyuanChina
  3. 3.Department of Respiratory MedicineAffiliated Jiangyin Hospital of Southeast University Medical SchoolJiangyinChina
  4. 4.Department of Cardiovascular Surgery, Xijing HospitalFourth Military Medical UniversityXi’anChina
  5. 5.Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an Jiaotong University Health Science CenterXi’anChina
  6. 6.Department of Plastic and Cosmetic SurgeryGansu Provincial HospitalLanzhouChina
  7. 7.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of PhysiologyNanjing Medical UniversityNanjingChina

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