Resveratrol improves contractile dysfunction, cell viability and oxidative stress in adult rat cardiomyocytes exposed to norepinephrine via SOD/FOXO1

In heart failure, cardiac remodeling and dysfunction are driven by abnormalities of cardiomyocyte caused by excessive circulating norepinephrine (NE). This study examined resveratrol's effect on NE-exposed adult rat cardiomyocytes. NE-induced morphological changes in cardiomyocytes, that reduce viability and contractile dysfunction, an increase in the levels of an oxidative stress and decrease in the activity of the antioxidant enzyme, superoxide dismutase (SOD). Resveratrol blocked NE-induced anomalies, improving cell viability and contractile function. Our study also revealed that resveratrol-mediated cardiomyocyte protection was lost when antioxidant enzyme activity of SOD was pharmacologically blocked. In addition, the pharmacological blockade of transcription factor forkhead box protein O1 (FOXO1) resulted in the negation of resveratrol-facilitated beneficial effects. Resveratrol also reduced the cardiac fibroblast viability without affecting cell death. In conclusion, resveratrol protects adult rat cardiomyocytes from NE-induced abnormalities including oxidative stress partly via SOD/FOXO1. • Cardiac remodeling and dysfunction are driven by abnormalities of cardiomyocytes. • Elevated circulating norepinephrine (NE) plays a major role in heart failure. • NE also resulted in an increase in oxidative stress and decrease cell viability and contractile function. • Resveratrol protects adult rat cardiomyocytes from NE-induced abnormalities including oxidative stress via SOD/FOXO1.