Inhibitory effects of alpha-lipoic acid on oxidative stress in the rostral ventrolateral medulla in rats with salt-induced hypertension

Huang,Yu‑Peng; Jin,Hong‑Yan; Yu,Hui‑Ping

doi:10.3892/ijmm.2016.2846

Inhibitory effects of alpha-lipoic acid on oxidative stress in the rostral ventrolateral medulla in rats with salt-induced hypertension

Authors:
- Yu‑Peng Huang
- Hong‑Yan Jin
- Hui‑Ping Yu
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Affiliations: Department of Cardiovascular Medicine, Hanyang Hospital of Wuhan, Wuhan, Hubei 430050, P.R. China
Published online on: December 30, 2016 https://doi.org/10.3892/ijmm.2016.2846
Pages: 430-436

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Abstract

Oxidative stress in the rostral ventrolateral medulla (RVLM) plays an important role in the pathophysiology of hypertension. Alpha‑lipoic acid (ALA) is widely recognized for its potent superoxide inhibitory properties, and it can safely penetrate deep into the brain. The aim of this study was to explore whether ALA supplementation attenuates hypertensive responses and cardiac hypertrophy by decreasing the NAD(P)H oxidase (NOX)-derived overproduction of reactive oxygen species (ROS) in the mitochondria in the RVLM, and thus attenuating the development of salt‑induced hypertension. For this purpose, male Wistar rats were randomly divided into 2 groups and either fed a high-salt diet or not. After 8 weeks, the rats were either administered ALA or an equal volume of the vehicle for 8 weeks. The rats fed a high‑salt diet exhibited higher mean arterial pressure (MAP) and higher plasma noradrenaline (NE) levels, as well as cardiac hypertrophy, as evidence by the increased whole heart weight/body weight (WHW/BW) ratio, WHW/tibia length (TL) ratio and left‑ventricular weight (LVW)/TL ratio. Compared with the rats in the NS group, the rats in the HS group only exhibited increased levels of superoxide, NOX2, NOX4 and mitochondrial malondialdehyde (MDA), but also decreased levels of copper/zinc (Cu/Zn)-superoxide dismutase (SOD), mitochondrial SOD and glutathione (GSH) in the RVLM. The supplementation of ALA decreased MAP, plasma NE levels and the levels of cardiac hypertrophy indicators. It also decreased the levels of superoxide, NOX2, NOX4 and mitochondrial MDA, and increased the levels of Cu/Zn‑SOD, mitochondrial SOD and GSH in the RVLM compared with the rats fed a high-salt diet and not treated with ALA. On the whole, our findings indicate that long‑term ALA supplementation attenuates hypertensive responses and cardiac hypertrophy by decreasing the expression of NAD(P)H subunits (NOX2 and NOX4), increasing the levels of mitochondrial bioenergetic enzymes, and enhancing the intracellular antioxidant capacity in the RVLM during the development of hypertension.

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