title: Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension.
abstract: 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.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Yuh-Ing Junior College of Health Care &Management, Kaohsiung, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Cheng
authors.affiliation: Department of Diving Medicine, Zouying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
authors.forename: Hui-Chieh
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Institute of Clinical Medicine, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lai
authors.affiliation: Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Gwo-Ching
authors.initials: GC
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Tung-Chen
authors.initials: TC
authors.lastname: Yeh
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Section of Neurology, Kaohsiung Veterans General Hospital, Taiwan.
authors.forename: Yu-Te
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chun-Peng
authors.initials: CP
authors.lastname: Liu
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
authors.forename: Ching-Jiunn
authors.initials: CJ
authors.lastname: Tseng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001794:Blood Pressure; D004195:Disease Models, Animal; D020536:Enzyme Activators / Q000008:administration & dosage; D005632:Fructose / Q000008:administration & dosage*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D020536:Enzyme Activators; D017382:Reactive Oxygen Species; D013267:Stilbenes; D005632:Fructose; D055372:AMP-Activated Protein Kinases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D000077185:Resveratrol