Inhibitory effects of alpha-lipoic acid on oxidative stress in the rostral ventrolateral medulla in rats with salt-induced hypertension
Oxidative stress in the rostral ventrolateral medulla (RVLM) plays an important role in the pathophysiology of hypertension. Alphalipoic 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
saltinduced 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 highsalt 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 leftventricular 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/ZnSOD, 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 longterm 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.
Document Type: Research Article
Affiliations: Department of Cardiovascular Medicine, Hanyang Hospital of Wuhan, Wuhan, Hubei 430050, P.R. China
Publication date: 01 January 2017
- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases. - Editorial Board
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