Reduction in basal nitric oxide activity causes albuminuria.
Reduction in basal nitric oxide activity causes albuminuria.
复制标题
DOI：
10.2337/db09-1630
复制
发表时间：
2011-02
期刊：
影响因子：
7.7
通讯作者：
Schmieder RE
中科院分区：
文献类型：
--
作者：
Ott C;Schneider MP;Delles C;Schlaich MP;Schmieder RE
肾小球滤过器的屏障功能已经研究了几十年。白蛋白尿反映了这一屏障的功能障碍，在动物中，功能障碍的内皮一氧化氮（NO）合酶导致白蛋白尿。我们的目的是分析一氧化氮的肾小球屏障功能在人类的重要性。为了评估内皮功能障碍对白蛋白尿的影响，我们在两个不同的研究人群中测量了全身输注NG-单甲基-L-精氨酸（L-NMMA）阻断NO脱氢酶（NOS）之前和之后的尿白蛋白/肌酐比值（UACR）。在人群A中，62例高血压合并2型糖尿病患者，在人群B中，22例高胆固醇血症但无高血压或2型糖尿病患者接受了检查。所有受试者的肾功能均正常。在伴有2型糖尿病的高血压患者（研究人群A）和高胆固醇血症患者（研究人群B）中，UACR对l-NMMA抑制NOS的反应显著增加。线性回归分析显示，在两个人群中，即使在调整滤过分数后，平均动脉压对l-NMMA的反应变化与UACR对l-NMMA的反应增加无关。NOS抑制引起与血压变化无关的蛋白尿。值得注意的是，这一发现在易发生内皮功能障碍和蛋白尿的患者组中很明显。因此，内皮功能的急性恶化通过降低NO活性引起白蛋白尿的增加。
The barrier function of the glomerular filter has been studied for decades. Albuminuria reflects a malfunction of this barrier, and in animals dysfunctional endothelial nitric-oxide (NO) synthase results in albuminuria. We aimed to analyze the importance of NO for the glomerular barrier function in humans. To assess the effect of endothelial dysfunction on albuminuria, we measured the urine albumin-to-creatinine ratio (UACR) both before and after the blockade of NO synthases (NOSs) with systemic infusion of NG-monomethyl-l-arginine (l-NMMA) in two distinct study populations. In population A, 62 hypertensive patients with type 2 diabetes and, in population B, 22 patients with hypercholesterolemia but without hypertension or type 2 diabetes were examined. All subjects had normal renal function. There was a significant increase in the UACR in response to NOS inhibition with l-NMMA in hypertensive patients with type 2 diabetes (study population A) and in patients with hypercholesterolemia (study population B). Linear regression analyses revealed that the change in mean arterial presssure in response to l-NMMA was not related to the increase in the UACR in response to l-NMMA in either population, even after adjusting for filtration fraction. NOS inhibition provokes albuminuria that is unrelated to changes in blood pressure. It is noteworthy that this finding was evident in patient groups prone to endothelial dysfunction and albuminuria. Thus, acute deterioration of endothelial function by reducing NO activity causes an increase in albuminuria.