Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX-4 in female hormone deprivation rats
Document Type
Article
Publication Date
1-30-2025
Publication Title
Acta Physiologica
Abstract
Aim: Young women exhibit lower rates of cardiovascular disease (CVD) than age-matched men, a protective effect often attributed to estrogen's influence on cardiac and mitochondrial function. The risk of CVD increases in post-menopausal women, likely due to estrogen deficiency and aldosterone's negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health. We hypothesized that in estrogen-deprived conditions, aldosterone could stimulate NADPH oxidase, leading to mitochondrial dysfunction, and reduced cardiac contractility. Methods: Wistar rats were divided into four groups: Sham, Ovariectomy-induced hormone deprivation (Ovx), Ovx with apocynin treatment, and Ovx with spironolactone treatment for 60 days. Results: Both apocynin and spironolactone countered the adverse effects of hormone deprivation by preserving myocardial contractility, improving cellular responses to calcium and isoproterenol, and normalizing the expression of key mitochondrial proteins. These compounds also attenuated the increase in reactive oxygen species (ROS) and maintained mitochondrial respiration rates. Conclusion: We concluded that estrogen deficiency contributes to cardiac oxidative stress via the NADPH oxidase and mitochondrial pathways. Apocynin and spironolactone offer significant protective effects, opening new avenues for treating cardiac issues related to estrogen deficiency.
PubMed ID
39887519
Volume
241
Issue
3
Recommended Citation
Rodrigues, Samya Mere L.; Ximenes, Carolina F.; Rodrigues, Nathália; Ronconi, Karoline; Costa, Anna Karolina Nascimento; Vieira, Livia Barroca; da Silva, Maria Luiza Yago; Ferreira, Katyana K.S.; Eliezeck, Marcos; Scalzo, Sergio; Monteiro, André; Sanches, Bruno; Spalenza, Thiago; Fernandes, Aurélia Araújo; Guatimosim, Silvia; Varner, Kurt J.; Ribeiro, Eduardo Hertel; and Stefanon, Ivanita, "Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX-4 in female hormone deprivation rats" (2025). School of Medicine Faculty Publications. 3497.
https://digitalscholar.lsuhsc.edu/som_facpubs/3497
10.1111/apha.70007