Functional Cross-Talk Between Aldosterone and Angiotensin-(1-7) in Ventricular Myocytes
Functional Cross-Talk Between Aldosterone and Angiotensin-(1-7) in Ventricular Myocytes
复制标题
DOI：
10.1161/hypertensionaha.111.199539
复制
发表时间：
2013-02
期刊：
影响因子：
8.3
通讯作者：
Pedro W. Machado de Almeida;Ricardo de Freitas Lima;Enéas Ricardo de Morais Gomes;Cibele Rocha Resende;D. Roman-Campos;A. N. Gondim;Mariana Gavioli;Aline Lara;Amanda Parreira;Sasha Luísa de Azevedo Nunes;Márcia N M Alves;S. L. Santos;N. Alenina;M. Bader;R. Resende;J. dos Santos Cruz;R. A. Souza dos Santos;S. Guatimosim
中科院分区：
文献类型：
--
作者：
Pedro W. Machado de Almeida;Ricardo de Freitas Lima;Enéas Ricardo de Morais Gomes;Cibele Rocha Resende;D. Roman-Campos;A. N. Gondim;Mariana Gavioli;Aline Lara;Amanda Parreira;Sasha Luísa de Azevedo Nunes;Márcia N M Alves;S. L. Santos;N. Alenina;M. Bader;R. Resende;J. dos Santos Cruz;R. A. Souza dos Santos;S. Guatimosim
高血清醛固酮水平与心脏病的发生有关。相比之下，血管紧张素 (Ang)-(1-7) 被广泛证明具有心脏保护作用，包括减轻体内盐皮质激素过度激活引起的心脏功能障碍，这表明这两种分子之间可能存在相互作用。在这里，我们研究了醛固酮和 Ang-(1-7) 之间是否存在串扰及其对心室肌细胞中钙 (Ca2+) 信号传导的功能影响。在加载 Fluo-4/AM 的肌细胞中评估醛固酮对 Ca2+ 瞬态的短期影响。共焦图像显示Ang-(1-7)对Ca2+瞬变参数没有影响，而醛固酮增加了Ca2+瞬变的幅度。非常出乎意料的是，向醛固酮处理的心肌细胞中添加 Ang-(1-7) 进一步增强了 Ca2+ 瞬变的幅度，表明这些分子具有协同作用。醛固酮对 Ca2+ 瞬时振幅的作用是由蛋白激酶 A 介导的，并且与 Ca2+ 电流 (ICa) 密度的增加有关。这两个变化均未被 Ang-(1-7) 改变。当心肌细胞暴露于醛固酮时，测量到Ca2+火花率增加。 Ang-(1-7) 阻止了这种变化。此外，NO 合酶抑制剂恢复了醛固酮对 Ang-(1-7) 处理的心肌细胞中 Ca2+ 放电率的影响，并减弱了这 2 个分子对 Ca2+ 瞬变的协同作用。这些结果表明 NO 在这种串扰中起着重要作用。我们的研究结果为理解两种具有拮抗心脏作用的重要分子如何相互作用以协同放大心肌细胞中的 Ca2+ 信号带来了新的视角。
High serum levels of aldosterone have been linked to the development of cardiac disease. In contrast, angiotensin (Ang)-(1-7) was extensively shown to possess cardioprotective effects, including the attenuation of cardiac dysfunction induced by excessive mineralocorticoid activation in vivo, suggesting possible interactions between these 2 molecules. Here, we investigated whether there is cross-talk between aldosterone and Ang-(1-7) and its functional consequences for calcium (Ca2+) signaling in ventricular myocytes. Short-term effects of aldosterone on Ca2+ transient were assessed in Fluo-4/AM-loaded myocytes. Confocal images showed that Ang-(1-7) had no effect on Ca2+ transient parameters, whereas aldosterone increased the magnitude of the Ca2+ transient. Quite unexpectedly, addition of Ang-(1-7) to aldosterone-treated myocytes further enhanced the amplitude of the Ca2+ transient suggesting a synergistic effect of these molecules. Aldosterone action on Ca2+ transient amplitude was mediated by protein kinase A, and was related to an increase in Ca2+ current (ICa) density. Both changes were not altered by Ang-(1-7). When cardiomyocytes were exposed to aldosterone, increased Ca2+ spark rate was measured. Ang-(1-7) prevented this change. In addition, a NO synthase inhibitor restored the effect of aldosterone on Ca2+ spark rate in Ang-(1-7)-treated myocytes and attenuated the synergistic effect of these 2 molecules on Ca2+ transient. These results indicate that NO plays an important role in this cross-talk. Our results bring new perspectives in the understanding of how 2 prominent molecules with supposedly antagonist cardiac actions cross-talk to synergistically amplify Ca2+ signals in cardiomyocytes.