Effects of valproic acid on sympathetic activity and left ventricularmyocardial remodelling in rats during pressure overload

Authors: YANG LIU, SIYU LI, ZHIGANG ZHANG, ZHANJUN LV, HUIJIE JIANG, XIAO TAN, FENGQUAN LIU

Abstract: Background/aim: Pressure overload induces cardiac remodelling and results in heart failure. Enhanced sympathetic outflow participates in the development of cardiac remodelling for the duration of pressure overload as an independent factor. Valproic acid has recently been shown to reduce neuronal injury and have antiinflammatory and antiapoptotic effects as a histone deacetylase inhibitor. We speculate that the drug plays a specific role in alleviating cardiac remodelling by inhibiting sympathetic activity. Materials and methods: Surgery of partial abdominal aortic constriction was performed on male Sprague-Dawley rats. After 4 weeks, animal models of pressure overload were validated and then valproic acid (300 mg/kg) was administrated to rats once a day for the next 4 weeks. Experimental parameters were detected 4 weeks after validation. Results: The administration of valproic acid alleviated cardiomyocyte hypertrophy, myocardial interstitial fibrosis and left ventricular diastolic dysfunction caused by partial abdominal aortic constriction. Valproic acid reduced the levels of plasma and local norepinephrine, augmented concentrations of hypothalamic gamma-aminobutyric acid, and had no side effects on the hepatic and renal function of the animals. Conclusion: These results suggest that valproic acid may be a safe and effective therapeutic strategy for the inhibition of sympathetic outflow and cardiac remodelling.

Keywords: Valproic acid, sympathetic activity, left ventricular myocardial remodelling, pressure overload, norepinephrine, gamma-aminobutyric acid

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