Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis
Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis
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DOI：
10.1038/sj.ki.5001983
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发表时间：
2006-12-01
影响因子：
19.6
通讯作者：
Wilcox, C.
中科院分区：
文献类型：
--
作者：
Aslam, S.;Santha, T.;Wilcox, C.
接受血液透析（HD）治疗的终末期肾病（ESRD）患者预期寿命明显缩短，这在很大程度上是由于心血管疾病（CVD），而不能用既定的危险因素来解释。我们检验了缬沙坦（一种血管紧张素受体阻滞剂）和氨氯地平（一种抗氧化钙通道阻滞剂）治疗可以降低氧化应激和血浆中不对称二甲基精氨酸（ADMA）水平（一种内源性一氧化氮合酶抑制剂）的假设。我们证实，与年龄和性别匹配的健康对照相比，ESRD患者有过度的氧化应激和精氨酸甲基化，其指标是血脂（13-羟基十八烯二烯酸（13-HODE））、硫醇（氧化：还原型谷胱甘肽、氧化谷胱甘肽（GSSG）： GSH）、蛋白质和核酸的血浆氧化产物水平升高，以及甲基化产物ADMA和对称二甲基精氨酸（SDMA）。我们进行了一项双盲交叉研究，分别用氨氯地平和缬沙坦进行6周的等效降压治疗，以检验我们的假设。两种处理均显著降低GSSG: GSH、8-羟基2-脱氧鸟苷、ADMA和SDMA水平，氨氯地平降低13-HODE。我们得出结论，高血压ESRD患者接受HD有证据表明脂质、硫醇、蛋白质和核酸的广泛氧化以及精氨酸的甲基化可能导致CVD。许多这些变化可以通过氨氯地平和缬沙坦的短期治疗来减轻。
Patients with end-stage renal disease ( ESRD) receiving hemodialysis (HD) treatment have a markedly shortened life expectancy in large part owing to cardiovascular disease (CVD), not explained by established risk factors. We tested the hypothesis that therapy with valsartan, an angiotensin receptor blocker and amlodipine, an antioxidant calcium channel blocker will reduce oxidative stress and the plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. We confirmed that compared with age- and gender-matched healthy controls, ESRD patients have excessive oxidative stress and arginine methylation as indexed by elevated plasma levels of oxidation products of lipids (13-hydroxyoctadecadienoic acid (13-HODE)), thiols ( oxidized: reduced glutathione, oxidized glutathione (GSSG): GSH), proteins, and nucleic acids, and the methylation products ADMA and symmetric dimethylarginine (SDMA). We undertook a double blind, crossover study of equi-antihypertensive treatment with amlodipine and valsartan for 6 weeks each to test our hypothesis. Both treatments significantly reduced GSSG: GSH, 8-hydroxy 2-deoxyguanosine, ADMA, and SDMA levels and amlodipine reduced 13-HODE. We conclude that hypertensive patients with ESRD receiving HD have evidence of extensive oxidation of lipids, thiols, proteins, and nucleic acids and methylation of arginine that could contribute to CVD. Many of these changes can be reduced by short-term treatment with amlodipine and valsartan.