Esaxerenone Attenuates Cardiac Hypertrophy in a Pressure Overload Model in Mice.

Abstract

Esaxerenone, a non-steroidal mineralocorticoid receptor (MR) blocker, exhibits high selectivity for MR. While clinically used as an anti-hypertensive drug, its impact on cardiac remodeling remains poorly understood. This study investigated the effect of esaxerenone on pressure overload-induced cardiac hypertrophy in mice.Eight-week-old C57BL/6 mice underwent either transverse aortic constriction (TAC) or sham surgery. Animals were divided into 2 groups: 0.003% (3.0 mg/kg) Esaxerenone-fed (EX) and normal-fed (CNT) groups (n = 64, Sham/CNT = 12, Sham/EX = 13, TAC/CNT = 18, TAC/EX = 21). Cardiac gene expressions were analyzed using quantitative real-time PCR.Food intake and body weight variations showed no significant differences between CNT and EX groups during the 2-week experimental period. The mortality rate from 24 hours after TAC surgery to the end of the experiment was 30.8% in the CNT group, however, all mice survived following TAC surgery in EX group. CNT group showed a remarkable increase in heart weight/tibial length ratio 2 weeks after TAC compared with the Sham group. The EX group demonstrated a significant decrease in HW/TL following TAC surgery (-23.4%, P = 0.041). Masson's trichrome staining revealed that the TAC/CNT group had a significantly higher proportion of fibrotic area than the Sham/CNT group. However, the TAC/EX group had a slightly lower proportion of fibrotic area than the TAC/CNT group. In cardiac gene expression analysis, ANP and Collagen 3a1 were upregulated in the TAC group but were significantly reduced following treatment with esaxerenone.Esaxerenone attenuates cardiac hypertrophy and hypertrophy-related gene expression, resulting in improved survival in a pressure overload model in mice.