Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

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 (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.

Resveratrol affects histone 3 lysine 27 methylation of vessels and blood biomarkers in DOCA salt-induced hypertension

“…In our study, acetylcholine-induced endothelium-dependent relaxations were decreased in the thoracic aorta isolated from the DOCA salt group similar to the previous report [15]. The beneficial action of resveratrol on relaxations of vessels isolated from spontaneously hypertensive and Dahl-salt sensitive rats has been examined [5][6][7]. However, the effect of resveratrol on the DOCA saltinduced decrease in the endothelium-dependent relaxations was not determined.…”

“…However, resveratrol increased plasma TAC levels of normotensive and hypertensive animals. The antioxidant properties of resveratrol were observed previously by other investigators using different hypertension models and durations [6,26].…”

“…Differences from control (*) and DOCA salt (?). Values are expressed as mean ± SEM (n = [8][9][10][11][12][13][14][15] reported [5][6][7]. In our study, DOCA salt-induced hypertension was prevented by resveratrol but, blood pressure of the normal animals was not affected.…”

“…In addition, resveratrol did not alter the plasma NO level in the current study. The preventive effect of resveratrol on hypertension-induced decreases in the NO level had been observed [6,20,21]. Because of the use of different experimental models and timing in hypertension, it is hard to compare that data and understand the nature of the NO level as a biomarker.…”

“…On the other hand, the beneficial effect of resveratrol on hypertension has been reported [4][5][6]. Resveratrol is a natural compound and has been found to have several pharmacological effects, including vasodilator, antiinflammatory, anti-platelet, anti-oxidant, anti-fungal, antiaging and anti-cancer properties [7].…”