慢性肾脏病患者急性内皮素-A受体拮抗后，蛋白尿和动脉僵硬度的降低与血压无关
Blood pressure-independent reduction in proteinuria and arterial stiffness after acute endothelin-a receptor antagonism in chronic kidney disease.
作者信息
Dhaun Neeraj, Macintyre Iain M, Melville Vanessa, Lilitkarntakul Pajaree, Johnston Neil R, Goddard Jane, Webb David J
机构信息
University of Edinburgh, Queen's Medical Research Institute, Royal Infirmary of Edinburgh, United Kingdom.
出版信息
Hypertension. 2009 Jul;54(1):113-9. doi: 10.1161/HYPERTENSIONAHA.109.132670. Epub 2009 Jun 8.
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.
内皮素 -1 与慢性肾脏病及其相关心血管疾病的发生和发展有关。因此，我们研究了用 BQ -123 选择性拮抗内皮素 -A 受体对非糖尿病慢性肾脏病患者心血管风险的关键独立替代标志物（血压、蛋白尿和肾脏血流动力学、动脉僵硬度及内皮功能）的影响。在一项双盲、随机交叉研究中，22 名蛋白尿性慢性肾脏病患者在两个不同时间分别接受安慰剂或 BQ -123。其中 10 名受试者还接受硝苯地平（10 毫克）作为 BQ -123 降压效果的活性对照。给药后监测血压、脉搏波速度、血流介导的血管舒张、肾血流量和肾小球滤过率。BQ -123 可降低血压（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 治疗后蛋白尿（-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，但血流介导的血管舒张未改变。硝苯地平引起的血压和肾血流量变化与 BQ -123 相似。然而，BQ -123 降低蛋白尿（-38±3% 对 26±11%；P<0.001）和脉搏波速度（-9±1% 对 -3±1%；P<0.001）的程度比硝苯地平更大。在肾病患者的标准治疗基础上，选择性内皮素 -A 受体拮抗可降低血压、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降低部分独立于血压。如果长期维持，选择性内皮素 -A 受体拮抗可能会给慢性肾脏病患者带来心血管和肾脏方面的益处。
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