The mineralocorticoid receptor (MR) and its ligand aldosterone are the principal modulators of hormone-regulated renal sodium reabsorption. In addition to the kidney, there are several other cells and organs expressing MR, in which its activation mediates pathologic changes, indicating potential therapeutic applications of pharmacological MR antagonism. Steroidal MR antagonists have been used for decades to fight hypertension and more recently heart failure. New therapeutic indications are now arising, and nonsteroidal MR antagonists are currently under development. This review is focused on nonclassic MR targets in cardiac, vascular, renal, metabolic, ocular, and cutaneous diseases. The MR, associated with other risk factors, is involved in organ fibrosis, inflammation, oxidative stress, and aging; for example, in the kidney and heart MR mediates hormonal tissue-specific ion channel regulation. Genetic and epigenetic modifications of MR expression/activity that have been documented in hypertension may also present significant risk factors in other diseases and be susceptible to MR antagonism. Excess mineralocorticoid signaling, mediated by aldosterone or glucocorticoids binding, now appears deleterious in the progression of pathologies that may lead to end-stage organ failure and could therefore benefit from the repositioning of pharmacological MR antagonists.

中文翻译：

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盐皮质激素受体在病理学中的新兴作用：迈向临床药理学的新范式。

盐皮质激素受体（MR）及其配体醛固酮是激素调节肾钠重吸收的主要调节剂。除肾脏外，还有其他几种表达MR的细胞和器官，其激活介导病理变化，表明药理MR拮抗作用的潜在治疗应用。甾体MR拮抗剂已被用于抗击高血压和最近出现的心力衰竭。现在出现了新的治疗适应症，非类固醇MR拮抗剂也正在开发中。这项审查的重点是在心脏病，血管，肾脏，代谢，眼和皮肤疾病中的非经典MR目标。MR与其他危险因素有关，涉及器官纤维化，炎症，氧化应激和衰老。例如，在肾脏和心脏中，MR介导激素组织特异性离子通道调节。高血压中已证明的MR表达/活性的遗传和表观遗传修饰也可能是其他疾病的重要危险因素，并且易受MR拮抗作用。由醛固酮或糖皮质激素结合介导的过量盐皮质激素信号转导在病理学进展中似乎是有害的，可能导致终末期器官衰竭，因此可从药理性MR拮抗剂的重新定位中受益。