Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.
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 (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-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 -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.
UMR-S 769 Inserm, Univ Paris-Sud Châtenay-Malabry, Châtenay-Malabry, France.
Stéphanie
S
Rimbaud
Matthieu
M
Ruiz
Jérôme
J
Piquereau
Philippe
P
Mateo
Dominique
D
Fortin
Vladimir
V
Veksler
Anne
A
Garnier
Renée
R
Ventura-Clapier
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000150:complications*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D016019:Survival Analysis
D013267:Stilbenes; D000077185:Resveratrol