Abstract 007: Effects Of Finerenone - A Novel Non-steroidal Mineralocorticoid Receptor Antagonist In A Model Of Pressure Overload-induced Cardiac Hypertrophy

Abstract

Activation of mineralocorticoid receptors (MR) by its agonist aldosterone induces several unwanted processes like inflammation, fibrosis, increase of blood pressure and ventricular hypertrophy. Inversely, the blockade of MR is known as a highly efficacious therapy in chronic heart failure and arterial hypertension. Therapy with currently approved MR antagonists is often limited due to side effects. Recently, new highly selective, non-steroidal aldosterone antagonists such as finerenone have been developed. To investigate the effects of finerenone on progressive cardiac hypertrophy the transverse aortic constriction (TAC) model was used. C57BL/6 male mice underwent a TAC-operation and were treated daily by oral gavage with finerenone (fin; 10 mg/kg/d), eplerenone (200 mg/kg/d) or vehicle (veh). The treatment started one week before the TAC-operation, and was continued 4 weeks postoperative. To examine the efficacy of finerenone on myocardial wall thickening echocardiography was performed one week before and 4 weeks after TAC and left ventricular mass (LVM) was calculated. Furthermore, gene expression analysis in heart and kidney were carried out to investigate molecular mechanisms. TAC-operated mice treated with finerenone showed a significant lower LVM relative to body weight compared with vehicle-treated mice (fin: 3.89 mg/g; veh: 4.32 mg/g; p<0.05). Also the percentage increase of LVM four weeks after TAC was significantly lower in finerenone-treated animals than in vehicle-treated mice (fin: +37.16 %, veh: +52.9 %, p<0.05). Furthermore, markers of pathological hypertrophy like atrial natriuretic factor (ANF) and β-myosin heavy chain (β-MyHC) were measured in the left ventricle, and showed a higher expression in vehicle-treated than finerenone-treated animals. Treatment with eplerenone did not significantly reduce cardiac hypertrophy after 4 weeks post TAC. In conclusion, these data show for the first time beneficial effects of the new non-steroidal MR-antagonist finerenone on LVM development in a TAC-model. The distinct actions of finerenone when compared to eplerenone may result from different MR-blocking properties.