Cardioprotective Effects of Finerenone and Suppressed Myocardial Sodium Accumulation in Aldoster

04 Mar 20264 min read0 viewsJournal Feed

GIST

Journal of the American Heart Association, Volume 15, Issue 6 , March 17, 2026. BackgroundClinical 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.MethodsHere, 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.ResultsEchocardiographic 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.

Clinical Editorial

Context and objective

The study investigates how finerenone, a nonsteroidal mineralocorticoid receptor antagonist, contributes to cardiovascular protection and whether its effects relate to myocardial sodium handling and inflammation in a rat model.

Study design and population

Experimental model: uninephrectomy male Sprague-Dawley rats
Intervention: chronic aldosterone infusion (0.75 μg/h) with 1% NaCl in drinking water for 4 weeks to induce aldosterone/salt loading
Treatment group: finerenone given at 10 mg/kg
Comparators: aldosterone/salt-loaded rats without finerenone, plus presumably baseline controls (not specified in detail)

Key outcomes and findings

Cardiac structure and function: aldosterone/salt loading produced adverse remodeling and ventricular dysfunction with preserved ejection fraction; finerenone completely prevented this dysfunction.
Myocardial sodium content: left ventricular sodium accumulation was markedly elevated with aldosterone/salt loading and attenuated by finerenone treatment.
Macrophage response: aldosterone/salt loading increased cardiac macrophage recruitment and shifted toward M1 polarization; finerenone prevented macrophage migration and polarization.
In vitro macrophage signaling: in RAW264.7 cells, finerenone reduced aldosterone/salt-induced upregulation of M1 markers, with a tendency for M2 markers to rise, potentially linked to NFAT5 and IL-10 pathways.

Interpretation and implications

The protective effect of finerenone appears linked to suppression of left ventricular sodium accumulation and interruption of inflammatory macrophage activity in the heart.
By mitigating sodium overload and the ensuing inflammatory milieu, finerenone may prevent adverse remodeling and preserve cardiac function in this model.

Limitations and uncertainties

The report summarizes findings from a single animal model and in vitro macrophage experiments; translational relevance to humans remains to be established.
Specific quantitative metrics (e.g., exact echocardiographic parameters, effect sizes) are not provided in the summarized content.