Huang Yu-Peng, Jin Hong-Yan, Yu Hui-Ping
Department of Cardiovascular Medicine, Hanyang Hospital of Wuhan, Wuhan, Hubei 430050, P.R. China.
Int J Mol Med. 2017 Feb;39(2):430-436. doi: 10.3892/ijmm.2016.2846. Epub 2016 Dec 30.
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.
延髓头端腹外侧区（RVLM）的氧化应激在高血压的病理生理学中起重要作用。α-硫辛酸（ALA）因其强大的超氧化物抑制特性而被广泛认可，并且它能够安全地深入大脑。本研究的目的是探讨补充ALA是否通过减少RVLM中线粒体中烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）氧化酶（NOX）衍生的活性氧（ROS）过量产生，从而减轻高血压反应和心脏肥大，进而减缓盐诱导的高血压的发展。为此，将雄性Wistar大鼠随机分为2组，分别给予高盐饮食或正常饮食。8周后，大鼠分别给予ALA或等量的溶媒，持续8周。喂食高盐饮食的大鼠表现出更高的平均动脉压（MAP）和更高的血浆去甲肾上腺素（NE）水平，以及心脏肥大，表现为全心重量/体重（WHW/BW）比值、WHW/胫骨长度（TL）比值和左心室重量（LVW）/TL比值增加。与正常饮食组大鼠相比，高盐饮食组大鼠不仅RVLM中超氧化物、NOX2、NOX4和线粒体丙二醛（MDA）水平升高，而且铜/锌（Cu/Zn）超氧化物歧化酶（SOD）、线粒体SOD和谷胱甘肽（GSH）水平降低。补充ALA可降低MAP、血浆NE水平和心脏肥大指标水平。与喂食高盐饮食且未用ALA处理的大鼠相比，它还降低了RVLM中超氧化物、NOX2、NOX4和线粒体MDA水平，并提高了Cu/Zn-SOD、线粒体SOD和GSH水平。总体而言，我们的研究结果表明，在高血压发展过程中，长期补充ALA可通过降低NAD(P)H亚基（NOX2和NOX4）的表达、增加线粒体生物能酶水平以及增强RVLM中的细胞内抗氧化能力，来减轻高血压反应和心脏肥大。
