Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes
Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes
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DOI：
10.1210/en.2002-220956
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发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Pratt, JH
中科院分区：
文献类型：
--
作者：
Chun, TY;Bloem, LJ;Pratt, JH
在动物研究中，醛固酮的增加与心肌坏死和纤维化有关，使用醛固酮的拮抗剂螺内酯治疗可以改善心力衰竭患者的临床结果。在目前的研究中，我们探索了一氧化氮(NO)，一种参与心脏功能的信号分子，作为醛固酮对心脏影响的潜在中介。体外培养的乳鼠心肌细胞经IL-1处理后，其诱导型一氧化氮合酶(INOS)和一氧化氮的水平均随醛固酮或地塞米松浓度的增加而降低。螺内酯增加iNOS的表达并阻止醛固酮的抑制，这与盐皮质激素受体介导的iNOS下调的机制一致。醛固酮对iNOS mRNA水平无影响，提示其抑制iNOS的机制可能是转录后机制。使用特定抗体中和转化生长因子-β1可逆转依赖于醛固酮的iNOS和NO下调。综上所述，醛固酮通过依赖转化生长因子-β1的机制在转录后抑制IL-1诱导的iNOS表达。NO合成的减少可能与已知的醛固酮的心脏效应有关。
In studies of animals, increases in aldosterone are associated with myocardial necrosis and fibrosis, and treatment with spironolactone, an antagonist of aldosterone, improved clinical outcomes in patients with heart failure. In the present study, we explored nitric oxide ( NO), a signaling molecule involved in cardiac function, as a potential mediator of aldosterone's effects on the heart. Levels of both inducible NO synthase ( iNOS) and NO from isolated rat neonatal cardiomyocytes pretreated with IL-1 were found to be decreased with exposure to aldosterone or dexamethasone in a dose-dependent manner. Spironolactone increased iNOS expression and prevented inhibition by aldosterone, consistent with a mineralocorticoid receptor-mediated mechanism for iNOS down-regulation. Aldosterone had no effect on iNOS mRNA levels, indicating a posttranscriptional mechanism for the inhibition of iNOS. Neutralization of TGF-beta1 using a specific antibody reversed aldosterone-dependent iNOS and NO down-regulation. In summary, aldosterone inhibited IL-1-induced iNOS expression posttranscriptionally by a TGF-beta1-dependent mechanism. The decrease in NO synthesis could have relevance to known cardiac effects of aldosterone.