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Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus.
Neurosci Bull 2019; 35(1):57-66NB

Abstract

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.

Authors+Show Affiliations

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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China. Department of Respiratory Medicine, Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin, 214400, China.Department of Plastic and Cosmetic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China.Department of Cardiology, Second Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Cardiology, Second Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, China.Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China. lyinxian777@mail.xjtu.edu.cn.Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.Department of Cardiology, Second Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, China. zhimingyang800@sina.com.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 Diseases, Xi'an Jiaotong University, Xi'an, 710061, China. ykang@mail.xjtu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30426340

Citation

Yu, Xiao-Jing, et al. "Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension Via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus." Neuroscience Bulletin, vol. 35, no. 1, 2019, pp. 57-66.
Yu XJ, Zhao YN, Hou YK, et al. Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus. Neurosci Bull. 2019;35(1):57-66.
Yu, X. J., Zhao, Y. N., Hou, Y. K., Li, H. B., Xia, W. J., Gao, H. L., ... Kang, Y. M. (2019). Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus. Neuroscience Bulletin, 35(1), pp. 57-66. doi:10.1007/s12264-018-0308-5.
Yu XJ, et al. Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension Via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus. Neurosci Bull. 2019;35(1):57-66. PubMed PMID: 30426340.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus. AU - Yu,Xiao-Jing, AU - Zhao,Ya-Nan, AU - Hou,Yi-Kang, AU - Li,Hong-Bao, AU - Xia,Wen-Jie, AU - Gao,Hong-Li, AU - Liu,Kai-Li, AU - Su,Qing, AU - Yang,Hui-Yu, AU - Liang,Bin, AU - Chen,Wen-Sheng, AU - Cui,Wei, AU - Li,Ying, AU - Zhu,Guo-Qing, AU - Yang,Zhi-Ming, AU - Kang,Yu-Ming, Y1 - 2018/11/14/ PY - 2018/04/11/received PY - 2018/09/26/accepted PY - 2020/02/01/pmc-release PY - 2018/11/15/pubmed PY - 2019/4/10/medline PY - 2018/11/15/entrez KW - Hypertension KW - Metformin KW - Oxidative stress KW - Paraventricular nucleus KW - Sympathoexcitation SP - 57 EP - 66 JF - Neuroscience bulletin JO - Neurosci Bull VL - 35 IS - 1 N2 - 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. SN - 1995-8218 UR - https://www.unboundmedicine.com/medline/citation/30426340/Chronic_Intracerebroventricular_Infusion_of_Metformin_Inhibits_Salt_Sensitive_Hypertension_via_Attenuation_of_Oxidative_Stress_and_Neurohormonal_Excitation_in_Rat_Paraventricular_Nucleus_ L2 - https://dx.doi.org/10.1007/s12264-018-0308-5 DB - PRIME DP - Unbound Medicine ER -