Blood Pressure-Independent Reduction in Proteinuria and Arterial Stiffness After Acute Endothelin-A Receptor Antagonism in Chronic Kidney Disease
Blood Pressure-Independent Reduction in Proteinuria and Arterial Stiffness After Acute Endothelin-A Receptor Antagonism in Chronic Kidney Disease
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DOI：
10.1161/hypertensionaha.109.132670
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发表时间：
2009-07-01
期刊：
影响因子：
8.3
通讯作者：
Webb, David J.
中科院分区：
文献类型：
--
作者：
Dhaun, Neeraj;MacIntyre, Iain M.;Webb, David J.
内皮素 1 与慢性肾脏疾病和相关心血管疾病的发生和进展有关。因此，我们研究了 BQ-123 选择性内皮素 A 受体拮抗作用对非糖尿病慢性肾病患者心血管风险的关键独立替代标志物（血压、蛋白尿和肾血流动力学、动脉僵硬度和内皮功能）的影响。在一项双盲、随机交叉研究中，22 名患有蛋白尿慢性肾病的受试者在 2 个不同的场合接受了安慰剂或 BQ-123。其中 10 名受试者还接受硝苯地平 (10 mg) 作为 BQ-123 抗高血压作用的活性对照。给药后监测血压、脉搏波速度、血流介导的扩张、肾血流量和肾小球滤过率。 BQ-123 降低血压（平均动脉压：-7 +/- 1%；与安慰剂相比，P < 0.001）并增加肾血流量（17 +/- 4%；与安慰剂相比，P < 0.01）。肾小球滤过率保持不变。 BQ-123 后，蛋白尿（-26 +/- 4%；与安慰剂相比，P < 0.01）和脉搏波速度（-5 +/- 1%；与安慰剂相比，P < 0.001）下降，但血流介导的扩张没有改变。硝苯地平与 BQ-123 观察到的血压和肾血流量变化相匹配。尽管如此，BQ-123 比硝苯地平更大程度地降低了蛋白尿（-38 +/- 3% 对比 26 +/- 11%；P < 0.001）和脉搏波传播速度（-9 +/- 1% 对比 -3 +/- 1%；P < 0.001）。在肾脏病患者的标准治疗基础上，选择性内皮素 A 受体拮抗剂可降低血压、蛋白尿和动脉僵硬度。此外，这些研究表明蛋白尿和动脉僵硬度的减少部分与血压无关。如果长期维持，选择性内皮素 A 受体拮抗作用可能会给慢性肾病患者的心血管和肾脏带来益处。 （高血压。2009；54：113-119。）
Endothelin 1 is implicated in the development and progression of chronic kidney disease and associated cardiovascular disease. We, therefore, studied the effects of selective endothelin-A receptor antagonism with BQ-123 on key independent surrogate markers of cardiovascular risk (blood pressure, proteinuria and renal hemodynamics, arterial stiffness, and endothelial function) in patients with nondiabetic chronic kidney disease. In a double-blind, randomized crossover study, 22 subjects with proteinuric chronic kidney disease received, on 2 separate occasions, placebo or BQ-123. Ten of these subjects also received nifedipine (10 mg) as an active control for the antihypertensive effect of BQ-123. Blood pressure, pulse wave velocity, flow-mediated dilation, renal blood flow, and glomerular filtration rate were monitored after drug dosing. BQ-123 reduced blood pressure (mean arterial pressure: -7 +/- 1%; P < 0.001 versus placebo) and increased renal blood flow (17 +/- 4%; P < 0.01 versus placebo). Glomerular filtration rate remained unchanged. Proteinuria (-26 +/- 4%; P < 0.01 versus placebo) and pulse wave velocity (-5 +/- 1%; P < 0.001 versus placebo) fell after BQ-123, but flow-mediated dilation did not change. Nifedipine matched the blood pressure and renal blood flow changes seen with BQ-123. Nevertheless, BQ-123 reduced proteinuria (-38 +/- 3% versus 26 +/- 11%; P < 0.001) and pulse wave velocity (-9 +/- 1% versus -3 +/- 1%; P < 0.001) to a greater extent than nifedipine. Selective endothelin-A receptor antagonism reduced blood pressure, proteinuria, and arterial stiffness on top of standard treatment in renal patients. Furthermore, these studies suggest that the reduction in proteinuria and arterial stiffness is partly independent of blood pressure. If maintained longer term, selective endothelin-A receptor antagonism may confer cardiovascular and renal benefits in patients with chronic kidney disease. (Hypertension. 2009; 54: 113-119.)