The involvement of aldosterone in cyclic stretch-mediated activation of NADPH oxidase in vascular smooth muscle cells
The involvement of aldosterone in cyclic stretch-mediated activation of NADPH oxidase in vascular smooth muscle cells
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DOI：
10.1038/hr.2009.76
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发表时间：
2009-08-01
影响因子：
5.4
通讯作者：
Sasaguri, Toshiyuki
中科院分区：
文献类型：
--
作者：
Ohmine, Takahiro;Miwa, Yoshikazu;Sasaguri, Toshiyuki
越来越多的证据表明醛固酮与心血管疾病的发病机制有关。我们检查了醛固酮是否有助于大鼠主动脉平滑肌细胞 (RASMC) 中循环拉伸 (CS) 诱导的活性氧 (ROS) 生成。将 RASMC 暴露于单轴 CS，然后收集以评估与醛固酮合成相关的 mRNA 或蛋白质的表达以及烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶活性。 CS 强度依赖性增强 NADPH 氧化酶活性。 CS 诱导细胞色素 P450 醛固酮合酶 (CYP11B2) 并增加醛固酮合成，但不影响 11 β-羟基类固醇脱氢酶 2 和盐皮质激素受体 (MR) 的水平。细胞外信号调节激酶 (ERK) 抑制剂 U0126 治疗几乎完全抑制了 CYP11B2 诱导，而血管紧张素 II (Ang II) 受体阻滞剂 (ARB) 奥美沙坦仅部分抑制 CS 诱导的 CYP11B2 表达和 ERK 磷酸化。选择性 MR 拮抗剂 eplerenone (10 lmol l(-1)) 即使在 ARB 存在的情况下也能显着减弱 CS 诱导的 NADPH 氧化酶活化。总之，醛固酮合成部分独立于 Ang II，可能在培养的 RASMC 中 CS 刺激的 ROS 生成中发挥重要作用。我们还提出了依普利农在治疗心血管疾病方面的潜在益处。高血压研究 (2009) 32, 690-699; doi：10.1038/hr.2009.76； 2009 年 5 月 29 日在线发布
Increasing evidence suggests that aldosterone is implicated in the pathogenesis of cardiovascular diseases. We examined whether aldosterone contributes to the cyclic stretch (CS)-induced reactive oxygen species (ROS) generation in rat aortic smooth muscle cells (RASMCs). RASMCs were exposed to uniaxial CS and thereafter collected to evaluate the expressions of mRNA or protein relating aldosterone synthesis and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. CS strength-dependently enhanced NADPH oxidase activity. CS induced cytochrome P450 aldosterone synthase (CYP11B2) and increased aldosterone synthesis but did not influence the levels of 11 beta-hydroxysteroid dehydrogenase 2 and mineralocorticoid receptor (MR). This CYP11B2 induction was almost completely suppressed by treatment with an extracellular signal-regulated kinase (ERK) inhibitor, U0126, whereas olmesartan, an angiotensin II (Ang II) receptor blocker (ARB), only partially suppressed CS-induced CYP11B2 expression and ERK phosphorylation. A selective MR antagonist, eplerenone (10 lmol l(-1)), significantly attenuated the CS-induced NADPH oxidase activation even in the presence of ARBs. In conclusion, aldosterone synthesis, which is partially independent of Ang II, may have an important role in CS-stimulated ROS generation in cultured RASMCs. We also suggest the potential benefit of eplerenone in the treatment of cardiovascular diseases. Hypertension Research (2009) 32, 690-699; doi:10.1038/hr.2009.76; published online 29 May 2009