title: Resveratrol via activation of AMPK lowers blood pressure in DOCA-salt hypertensive mice.
abstract: OBJECTIVE
  Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. Activation of AMPK induces vasorelaxation to lower blood pressure (BP). Whether resveratrol via activation of AMPK decreases, BP remains unknown.
  
  
  METHODS
  Male wild-type (WT) mice and mice deficient in AMPKα2 (AMPKα2(-/-)) were fed with resveratrol (400 mg/kg). After 7 d, mice were implanted with deoxycorticosterone acetate (DOCA)-salt (150 mg/kg) for 35 d. BP was detected by the radiotelemetry method. Vessel contraction was determined by organ chamber. Active RhoA, Rho-associated kinase (ROCK) activity, phosphorylations of myosin light chain (MLC), and myosin phosphatase targeting subunit 1 (MYPT1) were assayed by western blot.
  
  
  RESULTS
  Implantation of DOCA-salt dramatically increased systemic BPs (systolic BP and diastolic BP) in WT and AMPKα2(-/-) mice. However, treatment of resveratrol significantly decreased systemic BP in WT mice but not in AMPKα2(-/-) mice. In the organ chamber study, resveratrol inhibited agonist-induced vessel relaxation in WT mice aortas. Loss of AMPKα2 or AMPK inhibition by compound C reversed resveratrol-suppressed vasoconstriction in isolated mice aortas. In cultured vascular smooth muscle cells (VSMCs), activation of AMPK by resveratrol inhibited phenylephrine-enhanced MLC phosphorylation in a dose-dependent manner.
  
  
  CONCLUSIONS
  Resveratrol via activation of AMPK lowers BP in DOCA-hypertensive mice through an AMPK/RhoA/ROCK2/MLCMLC pathway.
authors.affiliation: a Department of Cardiovasology , The First Hospital of Jilin University , Changchun , China .
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Sun
authors.affiliation: b Medical College , Changchun , China , and.
authors.forename: Yu-Bo
authors.initials: YB
authors.lastname: Li
authors.affiliation: a Department of Cardiovasology , The First Hospital of Jilin University , Changchun , China .
authors.forename: Bing
authors.initials: B
authors.lastname: Du
authors.affiliation: c Department of Pathophysiology, Key Laboratory of Pathobiology , Ministry of Education, College of Basic Medicine, Jilin University , Changchun , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D064791:Desoxycorticosterone Acetate / Q000633:toxicity; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents
chemical_list: D016588:Anticarcinogenic Agents; D013267:Stilbenes; D014665:Vasodilator Agents; D064791:Desoxycorticosterone Acetate; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol
keywords: AMP-activated protein kinase; high blood pressure; resveratrol; vascular smooth muscle cells