Eplerenone suppresses aldosterone/salt-induced expression of NOX-4
Eplerenone suppresses aldosterone/salt-induced expression of NOX-4
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DOI：
10.1177/1470320310391330
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发表时间：
2011-09-01
影响因子：
2.9
通讯作者：
Eatman, Danita
中科院分区：
文献类型：
--
作者：
Bayorh, Mohamed A.;Rollins-Hairston, Aisha;Eatman, Danita
Dahl大鼠盐致高血压与血管紧张素II、醛固酮、自由基生成和内皮功能障碍的增加有关。然而，关于醛固酮对终末器官损伤作用的具体机制知之甚少。我们假设依普利酮通过阻断烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶活性来减轻肾损害。方法：分别饲喂低盐（LS）或高盐（HS）饮食的达尔盐敏感大鼠，在埃普利酮或罗布麻素存在的情况下给予醛固酮治疗。在饮食开始前测量间接血压，之后每周测量一次。治疗后测定血浆一氧化氮（NO）和尿8-异前列腺素水平。采用western blot法检测所选NADPH亚基的蛋白水平。结果：依普利酮和罗布麻素对HS和/或醛固酮所致的血压升高有抑制作用。这一观察结果伴随着肾脏NADPH氧化酶4 （NOX-4）和p22phox蛋白水平的平行变化。醛固酮和高盐与较低的NO水平和较大的肾脏氧化应激有关。结论：NADPH氧化酶与高盐饮食中观察到的血管和肾脏重构有关。醛固酮诱导的NOX-4表达在醛固酮的终末器官损伤效应中起关键作用，因为eplerenone倾向于减轻肾损伤并抑制NOX表达。
Introduction: Salt-induced hypertension in the Dahl rat is associated with increases in angiotensin II, aldosterone, free radical generation and endothelial dysfunction. However, little is known about the specific mechanism(s) associated with the end-organ damage effects of aldosterone. We hypothesised that eplerenone reduces kidney damage by blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.Methods: Dahl salt-sensitive rats fed either a low-salt (LS) or high-salt (HS) diet were treated with aldosterone in the presence of eplerenone or apocynin. Indirect blood pressure was measured prior to start of diet and weekly thereafter. Levels of plasma nitric oxide (NO) and urinary 8-isoprostane were measured following treatment. Protein levels of selected subunits of NADPH were assessed by western blot.Results: Eplerenone and apocynin inhibited the rise in blood pressure induced by HS and/or aldosterone. This observation was accompanied with a parallel change in kidney protein levels of NADPH oxidase 4 (NOX-4) and p22phox. Aldosterone and high salt were associated with lower NO levels and greater renal oxidative stress.Conclusions: NADPH oxidase is associated with the vascular and renal remodelling observed in high dietary salt intake. Aldosterone-induced expression of NOX-4 plays a pivotal role in the end-organ damage effect of aldosterone, as eplerenone tended to reduce kidney damage and inhibit NOX expression.