Cardioprotective Effects of Finerenone Associated With the Suppression of Myocardial Sodium Accumulation in Aldosterone/Salt‐Loaded Rats

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BACKGROUND: Clinical trials have indicated that finerenone, a nonsteroidal mineralocorticoid receptor antagonist, elicits considerable cardiovascular protective benefits; however, its precise mechanism of action remains to be fully elucidated. METHODS: Here, we examined the impact of finerenone on myocardial injury and sodium accumulation in uninephrectomy male Sprague-Dawley rats subjected to chronic aldosterone infusion (0.75 μg/h) and salt-loading (1% NaCl) in drinking water for 4 weeks. RESULTS: Echocardiographic assessments and gene expression analyses revealed adverse cardiac remodeling and ventricular dysfunction with preserved ejection fraction in aldosterone/salt-loaded uninephrectomy rats. Notably, finerenone (10 mg/kg) treatment completely prevented the development of cardiac dysfunction in these animals. Additionally, sodium content in left ventricular tissues was markedly elevated in aldosterone/salt-loaded uninephrectomy rats, which was attenuated by finerenone treatment. Furthermore, a significant increase in macrophage recruitment was observed in cardiac tissues with markedly elevated M1 macrophage populations. However, finerenone treatment effectively prevented migration as well as polarization of macrophage in cardiac tissue. In an in vitro assay using RAW264.7 cells, a macrophage cell line, finerenone dramatically reduced the aldosterone/salt-induced elevation of M1 markers, whereas M2 markers exhibited a tendency to increase, potentially linked to NFAT5 (nuclear factor of activated T-cells 5)- and IL (interleukin)-10-mediated pathways. CONCLUSIONS: These findings suggest that finerenone inhibits cardiac dysfunction induced by aldosterone/salt through the suppression of sodium accumulation in left ventricular tissues and attenuate subsequent macrophage-mediated inflammation, thereby preventing adverse cardiac remodeling and dysfunction.

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