Eplerenone is an orally active mineralocorticoid receptor (MR) antagonist that blocks the effects of aldosterone, with an IC50 value of 0.081μM[1, 2]. Eplerenone can be used in the study of hypertension, atherosclerosis, chronic systolic heart failure and cardiovascular diseases[3].
In vitro, Eplerenone (1µM) treatment of cardiomyocytes and fibroblasts for 24-48h promoted cardiomyocyte proliferation and increased cGMP activity[4]. Eplerenone (2µM) treatment of primary cultures of venous endothelial cells (EAHy 926) and human coronary artery endothelial cells (HCAEC) reversed aldosterone-induced endothelial cell growth and sclerosis in vitro[5].
In vivo, oral administration of Eplerenone (50mg/kg) to rats after unilateral ureteral obstruction (UUO) surgery inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration), interstitial cell proliferation and interstitial cell activation (α-SMA expression), and reduced oxidative stress[6]. Subcutaneous administration of Eplerenone (30mg/kg) to rats after unilateral hindlimb ischemia surgery significantly increased the number, colony formation and migration of endothelial progenitor cells (EPCs) after hindlimb ischemia, and decreased the expression of NAD(P)H oxidase p22 phox, p47 phox, gp91 phox and the expression of serum and glucocorticoid-induced aldosterone responsive kinase 1 (Sgk1)[7].
References:
[1] Coleman C I, Song J C, White C M. Eplerenone[J]. Formulary, 2002, 37(10): 514.
[2] Dhillon S. Eplerenone: a review of its use in patients with chronic systolic heart failure and mild symptoms[J]. Drugs, 2013, 73: 1451-1462.
[3] Funder J W. Eplerenone: hypertension, heart failure and the importance of mineralocorticoid receptor blockade[J]. Future Cardiology, 2006, 2(5): 535-541.
[4] Hermidorff M M, Faria G O, Amâncio G C S, et al. Non-genomic effects of spironolactone and eplerenone in cardiomyocytes of neonatal Wistar rats: do they evoke cardioprotective pathways?[J]. Biochemistry and Cell Biology, 2015, 93(1): 83-93.
[5] Hillebrand U, Schillers H, Riethmüller C, et al. Dose-dependent endothelial cell growth and stiffening by aldosterone: endothelial protection by eplerenone[J]. Journal of hypertension, 2007, 25(3): 639-647.
[6] Chen H, Sun F, Zhong X, et al. Eplerenone-mediated aldosterone blockade prevents renal fibrosis by reducing renal inflammation, interstitial cell proliferation and oxidative stress[J]. Kidney and Blood Pressure Research, 2013, 37(6): 557-566.
[7] Kobayashi N, Fukushima H, Takeshima H, et al. Effect of eplerenone on endothelial progenitor cells and oxidative stress in ischemic hindlimb[J]. American journal of hypertension, 2010, 23(9): 1007-1013.
Eplerenone（依普利酮）是一种具有口服活性的盐皮质激素受体（MR）拮抗剂，它的作用是阻断醛固酮的作用，IC50值为0.081μM[1, 2]。Eplerenone可用于高血压、动脉粥样硬化、慢性收缩期心力衰竭和心血管的研究[3]。
在体外，Eplerenone（1µM）处理心肌细胞和成纤维细胞24-48h，促进了心肌细胞增殖，并增加cGMP活性[4]。Eplerenone（2µM）处理静脉来源的内皮细胞系（EAHy 926）和人冠状动脉内皮细胞（HCAEC）的原代培养物，逆转了醛固酮在体外诱导的内皮细胞生长和硬化[5]。
在体内，Eplerenone（50mg/kg）通过口服治疗单侧输尿管梗阻（UUO）手术后的大鼠，抑制了肾纤维化、炎症（巨噬细胞和单核细胞浸润）、间质细胞增殖和间质细胞活化（α-SMA表达）的发展，并减少氧化应激[6]。Eplerenone（30mg/kg）通过皮下注射治疗诱导单侧后肢缺血手术后的大鼠，显著增加了大鼠后肢缺血后内皮祖细胞（EPC）的数量、集落形成和迁移，降低NAD(P)H 氧化酶p22 phox 、p47 phox 、gp91 phox的表达以及醛固酮效应激酶血清和糖皮质激素诱导的蛋白激1（Sgk1）的表达[7]。