Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Department of Microbiology and Hygiene, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh.
Int J Mol Sci. 2023 Jan 18;24(3):1922. doi: 10.3390/ijms24031922.
Inappropriate mineralocorticoid receptor (MR) activation in different cardiovascular cell types has deleterious effects on cardiac remodeling and function. Therefore, MR inhibition is a crucial pharmacological strategy to overcome cardiovascular dysfunction. Despite efficient blockade of MR with steroidal MR antagonists (MRAs), their clinical application is unsatisfactory due to the adverse effects. Newer non-steroidal MRAs with greater potency could be suitable for clinical application, especially in patients with type 2 diabetes mellitus and chronic kidney disease. Although clinical evidence has shown the beneficial effects of non-steroidal MRAs on cardiovascular outcomes in patients with heart failure with reduced ejection fraction, clinical trials are ongoing to evaluate the efficacy of heart failure with preserved ejection fraction. Therefore, comparative pharmacological characterization of non-steroidal MRAs over classic steroidal MRAs is crucial. Here, we summarize the pre-clinical evidence of non-steroidal MRAs, which suggests an improvement in cardiac dysfunction, as well as the underlying molecular mechanisms in animal models mimicking different clinical conditions. In addition, we discuss up-to-date information from clinical trials regarding the beneficial effects of non-steroidal MRAs on meaningful cardiovascular outcomes. Both pre-clinical and clinical evidence support treatment with non-steroidal MRAs in patients with cardiovascular disease.
在不同的心血管细胞类型中，不适当的盐皮质激素受体 (MR) 激活对心脏重构和功能有有害影响。因此，MR 抑制是克服心血管功能障碍的关键药理学策略。尽管用甾体 MR 拮抗剂 (MRAs) 有效地阻断了 MR，但由于不良反应，其临床应用并不令人满意。新型非甾体 MRA 具有更强的效力，可能适合临床应用，尤其是在 2 型糖尿病和慢性肾脏病患者中。尽管临床证据表明非甾体 MRA 对射血分数降低的心力衰竭患者的心血管结局有益，但仍在进行临床试验以评估射血分数保留的心力衰竭的疗效。因此，对非甾体 MRA 与经典甾体 MRA 的比较药理学特征进行描述至关重要。在这里，我们总结了非甾体 MRA 的临床前证据，这些证据表明在模拟不同临床情况的动物模型中，心脏功能障碍得到改善，以及潜在的分子机制。此外，我们还讨论了关于非甾体 MRA 对有意义的心血管结局有益影响的最新临床试验信息。临床前和临床证据都支持在心血管疾病患者中使用非甾体 MRA。
