Department of Pharmacology, Kagawa University Medical School, Japan.
J Pharmacol Sci. 2011;115(1):1-7. doi: 10.1254/jphs.10r07cr. Epub 2010 Dec 21.
Aldosterone, a steroid hormone, has traditionally been viewed as a key regulator of fluid and electrolyte homeostasis, as well as blood pressure, through the activation of mineralocorticoid receptor (MR). However, a number of studies performed in the last decade have revealed an important role of aldosterone/MR in the pathogenesis of renal injury. Aldosterone/MR-induced renal tissue injury is associated with increased renal inflammation and oxidative stress, fibrosis, mesangial cell proliferation, and podocyte injury, probably through genomic and non-genomic pathways. However, our preliminary data have indicated that acute administration of aldosterone or a selective MR antagonist, eplerenone, does not change blood pressure, heart rate, or renal blood flow. These data suggest that aldosterone/MR induces renal injury through mechanisms that are independent of acute changes in systemic and renal hemodynamics. In this review, we will briefly summarize the roles of aldosterone/MR in the pathogenesis of renal injury, focusing on the underlying mechanisms that are independent of systemic and renal hemodynamic changes.
醛固酮是一种类固醇激素，传统上被认为是通过激活盐皮质激素受体 (MR) 来调节体液和电解质平衡以及血压的关键激素。然而，过去十年中的多项研究揭示了醛固酮/MR 在肾损伤发病机制中的重要作用。醛固酮/MR 诱导的肾组织损伤与肾炎症和氧化应激增加、纤维化、系膜细胞增殖和足细胞损伤有关，可能通过基因组和非基因组途径。然而，我们的初步数据表明，急性给予醛固酮或选择性 MR 拮抗剂依普利酮不会改变血压、心率或肾血流量。这些数据表明，醛固酮/MR 通过独立于全身和肾脏血液动力学急性变化的机制诱导肾损伤。在这篇综述中，我们将简要总结醛固酮/MR 在肾损伤发病机制中的作用，重点介绍独立于全身和肾脏血液动力学变化的潜在机制。
