Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension

• Published in: Scientific reports 2016-05, Vol.6 (1), p.25342-25342, Article 25342
• Main Authors: Cheng, Pei-Wen, Lee, Hui-Chieh, Lu, Pei-Jung, Chen, Hsin-Hung, Lai, Chi-Cheng, Sun, Gwo-Ching, Yeh, Tung-Chen, Hsiao, Michael, Lin, Yu-Te, Liu, Chun-Peng, Tseng, Ching-Jiunn
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/51; 14; 14/19; 631/154/436; 692/699/75/243; 96; 96/31; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Antioxidants - administration & dosage; Blood Pressure; Disease Models, Animal; Enzyme Activators - administration & dosage; Extracellular signal-regulated kinase; Fructose; Fructose - administration & dosage; Humanities and Social Sciences; Hypertension; Hypertension - chemically induced; Hypertension - drug therapy; Kinases; Medulla oblongata; multidisciplinary; NAD(P)H oxidase; Oxidative stress; Phosphorylation; rac1 GTP-Binding Protein - metabolism; Rac1 protein; Rats, Inbred WKY; Reactive oxygen species; Reactive Oxygen Species - antagonists & inhibitors; Resveratrol; Ribosomal protein S6; Ribosomal protein S6 kinase; Rodents; Science; Stilbenes - administration & dosage; Superoxide dismutase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep25342

Recent studies have reported that the activation of AMP-activated protein kinase (AMPK) suppressed oxidative stress. The aim of this study was to examine whether the activation of AMPK in the brain decreased Rac1-induced ROS generation, thereby reducing blood pressure (BP) in rats with fructose-induced hypertension. The inhibition of ROS by treatment with an AMPK activator (oral resveratrol, 10 mg/kg/day) for 1 week decreased the BP and increased the NO production in the rostral ventrolateral medulla (RVLM) of fructose-fed rats but not in control Wistar-Kyoto (WKY) rats. In addition, resveratrol treatment abolished the Rac1-induced increases in the activity of the NADPH oxidase subunits p22-phox and reduced the activity of SOD2, while treatment with an AMPK inhibitor (compound C, 40 μM/day) had the opposite effect, in the fructose-fed rats. Interestingly, the activation of AMPK abolished Rac1 activation and decreased BP by inducing the activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and ribosomal protein S6 kinase (RSK) and nNOS phosphorylation in the fructose-fed rats. We conclude that the activation of AMPK decreased BP, abolished ROS generation and enhanced ERK1/2-RSK-nNOS pathway activity by negatively regulating Racl-induced NADPH oxidase levels in the RVLM during oxidative stress–associated hypertension.