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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.
- Source :
-
Neuroscience bulletin [Neurosci Bull] 2019 Feb; Vol. 35 (1), pp. 57-66. Date of Electronic Publication: 2018 Nov 14. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Antioxidants therapeutic use
Arterial Pressure drug effects
Hypertension chemically induced
Infusions, Intraventricular
Male
Metformin administration & dosage
Neurotransmitter Agents metabolism
Rats
Reactive Oxygen Species metabolism
Hypertension drug therapy
Metformin pharmacology
Oxidative Stress drug effects
Paraventricular Hypothalamic Nucleus drug effects
Sodium Chloride, Dietary pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1995-8218
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuroscience bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 30426340
- Full Text :
- https://doi.org/10.1007/s12264-018-0308-5