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首页> 外文期刊>American Journal of Physiology >Tetrahydrobiopterin lowers muscle sympathetic nerve activity and improves augmentation index in patients with chronic kidney disease
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Tetrahydrobiopterin lowers muscle sympathetic nerve activity and improves augmentation index in patients with chronic kidney disease

机译：四氢萘替替替林降低了肌肉交感神经活动，提高了慢性肾病患者的增强指数

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Chronic kidney disease (CKD) is characterized by overactivation of the sympathetic nervous system (SNS) that contributes to cardiovascular risk. Decreased nitric oxide (NO) bioavailability is a major factor contributing to SNS overactivity in CKD, since reduced neuronal NO leads to increased central SNS activity. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase that increases NO bioavailability in experimental models of CKD. We conducted a randomized, double-blinded, placebo-controlled trial testing the benefits of oral sapropterin dihydrochloride (6R-BH4, a synthetic form of BH4) in CKD. 36 patients with CKD and hypertension were randomized to 12 wk of 1) 200 mg 6R-BH4 twice daily + 1 mg folic acid once daily; vs. 2) placebo + folic acid. The primary endpoint was a change in resting muscle sympathetic nerve activity (MSNA). Secondary end-points included arterial stiffness using pulse wave velocity (PWV) and augmentation index (AIx), endothelial function using brachial artery flow-mediated dilation and endothelial progenitor cells, endothelium-independent vasodilatation (EID), microalbuminuria, and blood pressure. We observed a significant reduction in MSNA after 12 wk of 6R-BH4 (-7.5 ± 2.1 bursts/min vs. +3.2 ± 1.3 bursts/min; P = 0.003). We also observed a significant improvement in AIx (by -5.8 ± 2.0% vs. +1.8 ± 1.7 in the placebo group, P = 0.007). EID increased significantly (by +2.0 ± 0.59%; P = 0.004) in the 6R-BH4 group, but there was no change in endothelial function. There was a trend toward a reduction in diastolic blood pressure by - 4 ± 3 mmHg at 12 wk with 6R-BH4 (P = 0.055). 6R-BH4 treatment may have beneficial effects on SNS activity and central pulse wave reflections in hypertensive patients with CKD.
机译：慢性肾脏疾病（CKD）的特征是过度激活，有助于心血管风险的交感神经系统。一氧化氮（NO）降低（NO）生物利用度是有助于在CKD中的SNS过度效力有助于的主要因素，因为未降低的神经元没有导致中央SNS活性增加。四氢虫素（BH4）是一种必需的一氧化氮合酶，其在CKD的实验模型中没有增加生物利用度。我们进行了一种随机的双盲，安慰剂对照试验，测试口腔皂细胞素二盐酸盐（6R-BH4，BH4的合成形式的BH4）中的益处。 36例CKD和高血压患者随机分为12周，每日两次，每日两次+ 1mg叶酸; vs.2）安慰剂+叶酸。主要终点是静止肌肉交感神经活动（MSNA）的变化。次要终点包括使用脉搏波速度（PWV）和增强指数（AIX）的动脉刚度，使用肱动脉流动介导的扩张和内皮祖细胞，内皮尿血管细胞（EID），微白蛋白尿和血压的内皮功能。在6R-BH4（-7.5±2.1爆发/ min）后，我们观察到MSNA的显着降低（-7.5±2.1 / min + 3.2±1.3爆发/分钟; P = 0.003）。我们还观察到AIX的显着改善（安慰剂组中的-5.8±2.0％与+1.8±1.7，P = 0.007）。 EID在6R-BH4组中显着增加（+2.0±0.59％; p = 0.004），但内皮功能没有变化。在6R-BH4的12周下，舒张压血压降低了舒张压的趋势 - 4±3mmHg（P = 0.055）。 6R-BH4治疗可能对CKD高血压患者的SNS活性和中央脉冲波反射有益。

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