Abstract
The aim of this study was to examine the effects of finerenone, a nonsteroidal mineralocorticoid receptor (MR) antagonist, on myocardial injury and sodium accumulation in rats subjected to aldosterone and salt treatment. Finerenone was administered orally at a dose of 10 mg/kg body weight, while aldosterone was given subcutaneously at a rate of 0.75 μg/hr and salt was provided in drinking water at a concentration of 1% NaCl. Aldosterone-infused rats experienced mortality within 30 days, while finerenone-treated rats did not. Echocardiography and gene expression analyses were conducted to evaluate cardiac remodeling and function in rats exposed to salt/aldosterone loading for 4 weeks. The results showed adverse cardiac remodeling and cardiac dysfunction with preserved ejection fraction in these rats. However, finerenone treatment completely prevented cardiac dysfunction and improved cardiac remodeling. Sodium accumulation in the left ventricular tissues was markedly elevated in salt/aldosterone-loaded rats, but significantly reduced in rats treated with finerenone. Furthermore, finerenone treatment significantly reduced gene expression of F4/80, a macrophage marker. In vitro studies with RAW 264.7 cells showed that sodium treatment increased mRNA expression of pro-inflammatory markers and upregulated NFAT5, a transcription factor that regulates genes involved in osmotic stress, while reducing the expression of anti-inflammatory markers. Finerenone treatment suppressed the elevation of pro-inflammatory markers and NFAT5, but did not affect anti-inflammatory gene levels. These findings suggest that finerenone protects against aldosterone-induced myocardial injury by suppressing sodium accumulation and subsequent inflammation, as well as adverse cardiovascular remodeling.
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