Eplerenone–A novel Mineralocorticoid receptor antagonist for the clinical application

Abstract

Aldosterone is produced from the zona glomerulosa of the adrenal cortex in the adrenal gland, which is main mineralocorticoid hormone. Upon binding the mineralocorticoid receptor, it regulates sodium and potassium absorption, secretion, and retention, thereby maintaining stable blood pressure levels. However, abnormal aldosterone synthesis and metabolism could be pathogenic and contribute to multiple organ fibrosis and structural remodeling. For instance, hyperaldosteronemia is critically involved in the development of hypertension, heart failure (HF), and renal disease. Therefore, mineralocorticoid receptor antagonists (MRAs) that could fight against high concentrations of aldosterone play an important role in the treatment of diseases caused by hyperaldosteronism. Eplerenone, as a novel selective MRA, has better therapeutic efficiency and fewer side effects comparing to the classical drug spironolactone. In this review, first, we go through the biosynthesis and biologic properties of aldosterone and then introduce how hyperaldosteronemia facilitates certain diseases progression. Aldosterone is an important part of the renin-angiotensin-aldosterone system (RAAS), which plays a crucial role in essential hypertension, atrial tremor, and tissue fibrosis. Second, we summarize current evidence of clinical application of eplerenone in the control of primary aldosteronism, hypertension, HF, nephropathy, insulin resistance, and liver damage. It is exciting that many studies have shown that the use of eplerenone in these diseases yields good outcomes accompanied with fewer adverse effects such as hyperkalemia, metabolic acidosis, hypotension, and acute kidney failure, which indicates that eplerenone is a strong and safe MRA and inhibitor of RAAS system. This review focuses on therapeutic efficacy and disadvantages of eplerenone when treating a series of different diseases. Ultimately, we hope to shed light on future therapeutic strategies in diseases associated with hyperaldosteronemia.