Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Am J Physiol Heart Circ Physiol. 2012 Aug 15;303(4):H486-95. doi: 10.1152/ajpheart.00192.2012. Epub 2012 Jun 22.
The congestive heart failure (CHF) syndrome with soft tissue wasting, or cachexia, has its pathophysiologic origins rooted in neurohormonal activation. Mechanical cardiocirculatory assistance reveals the potential for reverse remodeling and recovery from CHF, which has been attributed to device-based hemodynamic unloading whereas the influence of hormonal withdrawal remains uncertain. This study addresses the signaling pathways induced by chronic aldosteronism in normal heart and skeletal muscle at organ, cellular/subcellular, and molecular levels, together with their potential for recovery (Recov) after its withdrawal. Eight-week-old male Sprague-Dawley rats were examined at 4 wk of aldosterone/salt treatment (ALDOST) and following 4-wk Recov. Compared with untreated, age-/sex-/strain-matched controls, ALDOST was accompanied by 1) a failure to gain weight, reduced muscle mass with atrophy, and a heterogeneity in cardiomyocyte size across the ventricles, including hypertrophy and atrophy at sites of microscopic scarring; 2) increased cardiomyocyte and mitochondrial free Ca(2+), coupled to oxidative stress with increased H(2)O(2) production and 8-isoprostane content, and increased opening potential of the mitochondrial permeability transition pore; 3) differentially expressed genes reflecting proinflammatory myocardial and catabolic muscle phenotypes; and 4) reversal to or toward recovery of these responses with 4-wk Recov. Aldosteronism in rats is accompanied by cachexia and leads to an adverse remodeling of the heart and skeletal muscle at organ, cellular/subcellular, and molecular levels. However, evidence presented herein implicates that these tissues retain their inherent potential for recovery after complete hormone withdrawal.
充血性心力衰竭（CHF）伴软组织消耗或恶病质的综合征，其病理生理起源源于神经激素激活。机械心脏循环辅助揭示了从 CHF 逆转重构和恢复的潜力，这归因于基于器械的血液动力学卸载，而激素撤退的影响仍不确定。本研究在器官、细胞/亚细胞和分子水平上研究了慢性醛固酮症在正常心脏和骨骼肌中诱导的信号通路，以及其在撤退后的恢复潜力（Recov）。在接受醛固酮/盐治疗（ALDOST）的 4 周和随后的 4 周 Recov 后，检查了 8 周龄雄性 Sprague-Dawley 大鼠。与未经处理的、年龄/性别/品系匹配的对照相比，ALDOST 伴有 1）体重增加失败，肌肉质量减少伴萎缩，心室之间的心肌细胞大小不均，包括微观瘢痕部位的肥大和萎缩；2）心肌细胞和线粒体游离 Ca(2+)增加，伴有氧化应激，H(2)O(2)产生和 8-异前列腺素含量增加，线粒体通透性转换孔开放电位增加；3）反映心肌和分解代谢肌肉表型的促炎基因表达差异；以及 4）4 周 Recov 后这些反应的逆转或向恢复的方向发展。大鼠的醛固酮症伴有恶病质，并导致心脏和骨骼肌在器官、细胞/亚细胞和分子水平上的不良重构。然而，本文提供的证据表明，这些组织在完全激素撤退后仍保留其内在的恢复潜力。
