title: Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice.
abstract: Resveratrol (RESV) is a polyphenol with pleiotropic effects that include reduction of oxidative stress and increased vascular nitric oxide (NO) production. However, whether or not RESV can prevent rises in blood pressure (BP) is controversial and remains to be firmly established. The purpose of this study was to determine whether RESV attenuates elevated BP and subsequent adaptive cardiac hypertrophy and to better understand the mechanisms involved. The spontaneously hypertensive rat (SHR) and the angiotensin (Ang)-II infused mouse were used as hypertensive models. Compared to a standard control diet, consumption of diets containing RESV by SHRs and Ang-II hypertensive mice, markedly prevented rises in systolic BP. In addition, flow-mediated vasodilation was significantly improved by RESV in SHRs. RESV also reduced serum and cardiac levels of the lipid peroxidation by-product, 4-hydroxy-2-nonenal in the hypertensive rodents and inhibited the production of superoxide in human-derived endothelial cells. Analysis of mesenteric arteries from SHRs and Ang-II infused mice demonstrated that RESV increased endothelial NO synthase (eNOS) phosphorylation by enhancing the LKB1/adenosine monophosphate (AMP)-activated protein kinase (AMPK) signal transduction pathway. Moreover, RESV reduced hypertrophic growth of the myocardium through reduced hemodynamic load and inhibition of the p70 S6 kinase pro-hypertrophic signaling cascade. Overall, we show that high dose RESV reduces oxidative stress, improves vascular function, attenuates high BP and prevents cardiac hypertrophy through the preservation of the LKB1-AMPK-eNOS signaling axis.
authors.affiliation: Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Vernon W
authors.initials: VW
authors.lastname: Dolinsky
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Pereira
authors.forename: Tatsujiro
authors.initials: T
authors.lastname: Oka
authors.forename: Jody
authors.initials: J
authors.lastname: Levasseur
authors.forename: Donna
authors.initials: D
authors.lastname: Beker
authors.forename: Beshay N
authors.initials: BN
authors.lastname: Zordoky
authors.forename: Jude S
authors.initials: JS
authors.lastname: Morton
authors.forename: Jeevan
authors.initials: J
authors.lastname: Nagendran
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control*; D002478:Cells, Cultured; D006801:Humans; D006973:Hypertension / Q000517:prevention & control*; D051379:Mice; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D013267:Stilbenes; D000077185:Resveratrol
keywords: 4-hydroxy-2-nonenal; AMP-activated protein kinase; AMPK; Ang-II; BP; HNE; HUVEC; HW/TL; Hypertension; IVRT; IVS; LV; LV ejection fraction; LV posterior wall; LVEF; LVPW; Left ventricular hypertrophy; Lipid peroxide; NO; Nitric oxide; RESV; ROS; Resveratrol; SHR; Signal transduction; angiotensin-II; blood pressure; eNOS; endothelial nitric oxide synthase; heart weight/tibia length; human umbilical vein endothelial cell; intraventricular relaxation time; intraventricular septum; left ventricular; nitric oxide; reactive oxygen species; resveratrol; spontaneously hypertensive rat