Menon Dileep V, Arbique Debbie, Wang Zhongyun, Adams-Huet Beverley, Auchus Richard J, Vongpatanasin Wanpen
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8586, USA.
J Clin Endocrinol Metab. 2009 Apr;94(4):1361-6. doi: 10.1210/jc.2008-2660. Epub 2009 Jan 21.
Previous studies in rats indicated that thiazide-type diuretics reduced blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory action in addition to diuretic effects.
The objectives were to determine effects of spironolactone and chlorthalidone on SNA and the role of SNA on diuretic-induced insulin resistance in human hypertension.
We conducted a randomized crossover study in 23 untreated hypertensive patients in which we measured muscle SNA at baseline, after 1 and 3 months of chlorthalidone (12.5-25 mg/d), and after 1 and 3 months of spironolactone (50-75 mg/d). Ambulatory BP, baroreflex sensitivity, and indices of insulin resistance were also assessed at baseline and after 3 months of each drug treatment.
Chlorthalidone caused a similar reduction in ambulatory BP from baseline when compared with spironolactone (11 +/- 2/4 +/- 2 and 10 +/- 2/4 +/- 2 mm Hg, respectively). However, chlorthalidone increased SNA by 23% (P < 0.01) within 1 month of treatment, whereas spironolactone had no effect in the same subjects. SNA continued to be elevated after 3 months of chlorthalidone when compared with baseline and spironolactone. Baroreflex control of SNA was unaffected by either drug. Chlorthalidone increased indices of insulin resistance, which were significantly correlated with increases in SNA from baseline, whereas spironolactone had no effect in the same subjects.
Our data suggest that chlorthalidone, the first-line drug therapy for hypertension, causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.
先前在大鼠中的研究表明，噻嗪类利尿剂可降低血压（BP）并引发压力反射介导的交感神经活动（SNA）增加，而螺内酯除利尿作用外还具有中枢性交感神经抑制作用。
本研究旨在确定螺内酯和氯噻酮对SNA的影响以及SNA在利尿剂诱导的人类高血压胰岛素抵抗中的作用。
我们对23例未经治疗的高血压患者进行了一项随机交叉研究，在基线时、氯噻酮（12.5 - 25mg/d）治疗1个月和3个月后以及螺内酯（50 - 75mg/d）治疗1个月和3个月后测量肌肉SNA。在基线时以及每种药物治疗3个月后还评估了动态血压、压力反射敏感性和胰岛素抵抗指标。
与螺内酯相比，氯噻酮使动态血压从基线水平有相似程度的降低（分别为11±2/4±2和10±2/4±2mmHg）。然而，氯噻酮在治疗1个月内使SNA增加了23%（P<0.01），而螺内酯对相同受试者无影响。与基线和螺内酯相比，氯噻酮治疗3个月后SNA持续升高。两种药物对SNA的压力反射控制均无影响。氯噻酮增加了胰岛素抵抗指标，且与基线时SNA的增加显著相关，而螺内酯对相同受试者无影响。
我们的数据表明，作为高血压一线药物治疗的氯噻酮会导致高血压患者交感神经系统持续激活和胰岛素抵抗。然而，尽管血压降低程度相似，但螺内酯可避免这些副作用。
