Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
Curr Opin Nephrol Hypertens. 2012 Mar;21(2):147-56. doi: 10.1097/MNH.0b013e32834fb25b.
The renal distal tubule has been considered for a long time as the main cellular target of aldosterone, where the hormone enhances sodium reabsorption and potassium secretion. However, other cell types in nonepithelial tissues, such as the heart, the vessels, adipose tissue, and macrophages, are now also recognized as targets for aldosterone. The functions that aldosterone exerts in these nonclassical target tissues are still a matter of debate. This review will highlight the recent findings on the extrarenal effects of aldosterone.
Numerous studies showed that aldosterone exerts profibrotic and proinflammatory effects, but one or more cofactors such as salt, angiotensin II, and oxidative stress are required. Moreover, inflammation and macrophage infiltration are a prerequisite to aldosterone-induced cardiac fibrosis. This underlines a key role for aldosterone and the mineralocorticoid receptor in macrophages. Inflammatory effects of aldosterone in vascular smooth muscle cells involve trafficking to lipid rafts/caveolae through receptor tyrosine kinases. Finally, a growing body of evidence indicates a prominent role of aldosterone/mineralocorticoid receptor in the metabolic syndrome, in insulin resistance, and in adipocyte biology.
The idiom from Socrates, 'the more we learn, the less we know', can be applied to aldosterone with its different facets and its pleiotropic effects. There is clear evidence for rapid nongenomic effects of aldosterone, mineralocorticoid receptor-dependent and mineralocorticoid receptor-independent signaling, in the heart, the vessels, and other nonepithelial tissues, leading to inflammation, fibrosis, and progression of cardiovascular diseases including hypertension and metabolic syndrome.
长期以来，人们一直认为醛固酮的主要靶细胞是肾脏远曲小管，该激素可增强钠重吸收和钾分泌。然而，现在人们也认识到心脏、血管、脂肪组织和巨噬细胞等非上皮组织中的其他细胞类型也是醛固酮的靶标。醛固酮在这些非经典靶组织中发挥的作用仍存在争议。这篇综述将重点介绍醛固酮在肾脏以外的作用的最新发现。
许多研究表明，醛固酮具有促纤维化和促炎作用，但需要盐、血管紧张素 II 和氧化应激等一个或多个协同因子。此外，炎症和巨噬细胞浸润是醛固酮诱导心脏纤维化的前提。这突显了醛固酮和盐皮质激素受体在巨噬细胞中的关键作用。醛固酮在血管平滑肌细胞中的炎症作用涉及通过受体酪氨酸激酶向脂筏/小窝易位。最后，越来越多的证据表明，醛固酮/盐皮质激素受体在代谢综合征、胰岛素抵抗和脂肪细胞生物学中起着重要作用。
用苏格拉底的名言“我们学得越多，就越明白自己的无知”来形容醛固酮再合适不过了，它有许多不同的方面和多种效应。醛固酮具有快速的非基因组效应，其作用依赖于盐皮质激素受体和不依赖于盐皮质激素受体的信号通路，可导致心脏、血管和其他非上皮组织中的炎症、纤维化和心血管疾病（包括高血压和代谢综合征）的进展。
