Internal Medicine, Department of Experimental and Clinical Medicine, University of Udine, Udine, Italy.
Horm Metab Res. 2012 Mar;44(3):181-7. doi: 10.1055/s-0031-1291318. Epub 2011 Nov 17.
Recent views suggest that long-term exposure to elevated aldosterone concentrations might result in cardiac, vascular, renal, and metabolic sequelae that occur independent of the blood pressure level. Indirect evidence of the untoward effects of aldosterone on the heart has been clearly established in clinical studies that have tested the effects of mineralocorticoid receptor antagonists in the treatment of systolic heart failure. As it has become clear in recent years, the interaction between aldosterone and the heart has to deal with additional actions of the hormone on specific cell types, cellular mechanisms, and molecules that are involved in regulation of tissue responses, leading to hypertrophy, remodeling, and fibrosis. The majority of these effects are mediated by activation of the mineralocorticoid receptors that are expressed in cardiomyocytes and cardiac fibroblasts, and mediate the genomic effects of the hormone. Evidence of interactions between aldosterone and the heart that occur independent of the renal effects of aldosterone, however, is not limited to the context of systolic heart failure and observations obtained in other disease states have led, together with findings of animal studies, to a better understanding of the potential benefits of aldosterone antagonists. In this narrative overview, we highlight the most recent findings that have been obtained in experimental animal models and in clinical conditions that include, in addition to systolic heart failure, primary aldosteronism, essential hypertension, diastolic heart failure, and arrhythmia.
最近的观点表明,长期暴露于升高的醛固酮浓度可能导致心脏、血管、肾脏和代谢的后果,这些后果独立于血压水平发生。在临床试验中,已经明确证实了醛固酮对心脏的不良影响,这些试验测试了盐皮质激素受体拮抗剂在治疗收缩性心力衰竭中的作用。近年来越来越清楚的是,醛固酮与心脏之间的相互作用必须涉及激素对特定细胞类型、细胞机制和参与调节组织反应的分子的额外作用,导致肥大、重构和纤维化。这些作用大多是通过在心肌细胞和心肌成纤维细胞中表达的矿物质皮质激素受体的激活介导的,这些受体介导激素的基因组作用。然而,醛固酮与心脏之间独立于醛固酮的肾作用的相互作用的证据不仅限于收缩性心力衰竭的情况,在其他疾病状态下的观察结果,以及动物研究的发现,导致了对醛固酮拮抗剂的潜在益处的更好理解。在本综述中,我们强调了在实验动物模型和临床条件下获得的最新发现,这些发现除了包括收缩性心力衰竭、原发性醛固酮增多症、原发性高血压、舒张性心力衰竭和心律失常外。