The Impact of Dapagliflozin on Aldosterone Hormone in Rats with Heart Failure

Abstract

Background: The latest anti-diabetic medication sodium-glucose co-transporter inhibitor along with the lowering of blood glucose has a cardioprotective and reno-protective effect, it has the ability to reduce the development of heart failure and decrease hospitalization in heart failure subjects with and without diabetes. This study was conducted to evaluate the effect of sodium-glucose co-transporter inhibitor dapagliflozin alone and in combination with eplerenone on the aldosterone hormone in the treatment of rats with experimentally induced heart failure.Method: Thirty Wister rats were randomly divided into five groups each of six rats, the first group served as a control group. The heart failure model was induced experimentally by intraperitoneal injection of isoprenaline 5mg/kg/day for one week for the rest of the experimental rat groups. The second group was a positive control. The third, fourth, and fifth groups received oral daily doses of dapagliflozin 10 mg/kg/day, eplerenone 100 mg/kg/day, and dapagliflozin-eplerenone 10,100 mg/kg/day respectively for four weeks.Results: Induction of heart failure in rats has significantly raised circulating BNP, NT-Pro BNP, aldosterone, troponin I, serum urea, and creatinine. Rats treated with dapagliflozin showed statistically significant decreases in BNP, NT-Pro BNP, aldosterone, troponin I, blood urea nitrogen, and serum creatinine. Non significant changes are seen in decreasing mean blood pressure. Dapagliflozin-eplerenone administration produced a significant reduction in plasma aldosterone level, heart rate, and diastolic blood pressure.Conclusion: The study demonstrates the cardiovascular benefit of sodium-glucose co transporter inhibitor dapagliflozin in rats with experimentally induced heart failure, reducing the myocardial stretch indicates the prominent role of dapagliflozin in reducing the development of heart failure and decreasing cardiovascular complications in subjects with and without diabetes. Moreover, the impact of dapagliflozin on renal function further contributes to cardiovascular benefits by reducing volume overload and neurohormonal activation which are features of cardiorenal syndrome.