aDepartment of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
J Hypertens. 2013 Feb;31(2):393-403. doi: 10.1097/HJH.0b013e32835b6c02.
The objective of this study is to determine the effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension.
A randomized, four-way, double-blind, crossover study in 31 adults with previously untreated obesity-related hypertension, in which the effects of 8 weeks' inhibition of the renin-angiotensin-aldosterone system (using aliskiren 300 mg), sympathoinhibition (using moxonidine 0.4 mg), diuretic therapy (using hydrochlorothiazide 25 mg) or placebo on flow-mediated dilation and 24-h blood pressure were compared.
The median flow-mediated dilation during placebo was 4.0% [interquartile range (IQR) 2.9-5.5%] and was increased by aliskiren [0.81%, 95% confidence interval (CI) 0.02-1.79], but not by moxonidine (0.20%, 95% CI -0.46 to 1.03) or hydrochlorothiazide (0.39%, 95%CI -0.31%-1.26%). Similarly, compared with placebo, mean 24-h blood pressure was most reduced by aliskiren (-9.8/-6.3 mmHg) and to a lesser degree by hydrochlorothiazide (-5.9/-2.6 mmHg). Moxonidine did not significantly affect blood pressure despite reduction of muscle sympathetic nerve activity. Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine. Unlike aliskiren and moxonidine, hydrochlorothiazide reduced urinary 8-iso-prostaglandin F2α-VI, a marker of oxidative stress. Vascular stiffness, systemic inflammation, leptin, adiponectin and other oxidative stress markers (plasma malondialdehyde, myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine) were unaffected by treatment.
Renin inhibition, but not sympathoinhibition or diuretic therapy, improves endothelial function and results in larger reductions of 24-h, office, and central blood pressure in obesity-related hypertension. This adds weight to the hypothesis that inhibition of the renin-angiotensin-aldosterone system is an effective first step in the treatment of obesity-related hypertension.
本研究旨在确定肾素-血管紧张素-醛固酮系统抑制、交感神经抑制和利尿剂治疗对肥胖相关高血压患者内皮功能和血压的影响。
对 31 例未经治疗的肥胖相关高血压患者进行了一项随机、四向、双盲、交叉研究，比较了 8 周肾素-血管紧张素-醛固酮系统抑制（使用阿利克仑 300mg）、交感神经抑制（使用莫索尼定 0.4mg）、利尿剂治疗（使用氢氯噻嗪 25mg）或安慰剂对血流介导的扩张和 24 小时血压的影响。
安慰剂期间的中位血流介导的扩张率为 4.0%（四分位间距 2.9-5.5%），阿利克仑增加了 0.81%（95%置信区间 0.02-1.79%），但莫索尼定没有增加（0.20%，95%置信区间-0.46 至 1.03%）或氢氯噻嗪（0.39%，95%置信区间-0.31%至 1.26%）。同样，与安慰剂相比，阿利克仑（-9.8/-6.3mmHg）和氢氯噻嗪（-5.9/-2.6mmHg）使 24 小时平均血压降低最多，而莫索尼定则没有明显影响血压，尽管它降低了肌肉交感神经活动。尽管盐酸噻嗪降低了肌肉交感神经活动，但在盐酸噻嗪治疗期间，胰岛素敏感性恶化，而阿利克仑或莫索尼定则不受影响。与阿利克仑和莫索尼定不同，氢氯噻嗪降低了氧化应激标志物 8-异前列腺素 F2α-VI（尿液）。血管僵硬、全身炎症、瘦素、脂联素和其他氧化应激标志物（血浆丙二醛、髓过氧化物酶活性和尿液 8-羟基脱氧鸟苷）不受治疗影响。
肾素抑制，而不是交感神经抑制或利尿剂治疗，可改善内皮功能，并导致肥胖相关高血压患者 24 小时、诊室和中心血压的更大降低。这进一步支持了肾素-血管紧张素-醛固酮系统抑制是肥胖相关高血压治疗的有效第一步的假说。
