Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus
1Department 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
2Department of Cardiology, Second Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, China
3Department of Respiratory Medicine, Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400, China
4Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
5Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
6Department of Plastic and Cosmetic Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
7Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029, China
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.
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