Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure 英文参考文献.docVIP

ResveratrolImprovesSurvival,Hemodynamicsand EnergeticsinaRatModelofHypertensionLeadingto HeartFailure Ste′phanieRimbaud1,2,MatthieuRuiz1,2,Je′ro?mePiquereau1,2,PhilippeMateo1,2,DominiqueFortin1,2 , VladimirVeksler1,2,AnneGarnier1,2,Rene′eVentura-Clapier1,2 * 1UMR-S769Inserm,UnivParis-SudCha?tenay-Malabry, Cha?tenay-Malabry, France,2UnivParis-Sud,IFR141,Cha?tenay-Malabry, France Abstract Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (whichoccurred3weeksaftersaltaddition).Resveratroltreatmentimprovedsurvival(64%inHS-RSVversus15%inHS-NT, p,0.001), and prevented the 25% reduction in body weight in HS-NT (P,0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening 234% in HS-NT) as evaluated by echocardiography, which occurredwithoutregressionofhypertensionorhypertrophy.Moreover,aorticendothelialdysfunctionpresentinHS-NTwas prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARa (peroxisome proliferator-activated receptor a) expression.Weconcludethatresveratroltreatmentexertsbeneficialprotectiveeffectsonsurvival,endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activatorscouldbearelevanttherapyinhypertension-inducedHF. Citation: Rimbaud S, Ruiz M, Piquereau J, Mateo P, Fortin D, e