Ruzicka Marcel, Coletta Elizabeth, Leenen Frans H H
Hypertension Unit, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Am J Hypertens. 2007 Nov;20(11):1202-8. doi: 10.1016/j.amjhyper.2007.05.014.
Angiotensin II-mediated increases in sympathetic activity may contribute to smaller blood-pressure decreases in response to dihydropyridines in young versus older hypertensive patients. We evaluated whether quinapril unmasks angiotensin II-dependent sympathetic activity on amlodipine.
In this double-blind, randomized, clinical trial, young mild hypertensives were randomized to quinapril for 1 week (study 1), followed by quinapril + amlodipine for 6 weeks (study 2), followed by amlodipine + placebo for 6 weeks (study 3), or else were randomized to placebo for 1 week (study 1), followed by placebo + amlodipine for 6 weeks (study 2), followed by amlodipine + quinapril for 6 weeks (study 3). Muscle sympathetic nerve activity (MSNA) and plasma hormones were analyzed at the end of each treatment period. Twenty-one subjects completed this study.
Quinapril alone decreased BP by 8 +/- 3/6 +/- 3 (mean +/- SD) mm Hg, and amlodipine alone decreased BP by 6 +/- 3/4 +/- 2 (mean +/- SD). Quinapril combined with amlodipine caused a drop of 13 +/- 3/13 +/- 3 (mean +/- SD) mm Hg in one group, and 14 +/- 3/14 +/- 2 (mean +/- SD) mm Hg in the second group. Six weeks after discontinuation of quinapril, amlodipine alone caused no change (0 +/- 3/-2 +/- 3) (mean +/- SD). The MSNA decreased by 3 bursts/100 heartbeats at visits 2 v 1 and 3 v 2 (P = .02 for time effect), regardless of treatment. Angiotensin II showed small increases with each visit in the first group, and small decreases in the second group (P = .02 for treatment effect).
It appears that amlodipine does not activate the renin-angiotensin system to counteract its BP-lowering effect in young hypertensives. Similarly, no angiotensin II-dependent component in MSNA appears to be present at baseline or to be induced by amlodipine.
血管紧张素II介导的交感神经活性增加可能导致年轻高血压患者与老年高血压患者相比，对二氢吡啶类药物的血压降低反应较小。我们评估了喹那普利是否会揭示氨氯地平对血管紧张素II依赖性交感神经活性的影响。
在这项双盲、随机临床试验中，年轻轻度高血压患者被随机分为接受喹那普利治疗1周（研究1），随后接受喹那普利+氨氯地平治疗6周（研究2），再接受氨氯地平+安慰剂治疗6周（研究3）；或者被随机分为接受安慰剂治疗1周（研究1），随后接受安慰剂+氨氯地平治疗6周（研究2），再接受氨氯地平+喹那普利治疗6周（研究3）。在每个治疗期结束时分析肌肉交感神经活动（MSNA）和血浆激素。21名受试者完成了这项研究。
单独使用喹那普利使血压降低8±3/6±3（均值±标准差）mmHg，单独使用氨氯地平使血压降低6±3/4±2（均值±标准差）mmHg。喹那普利与氨氯地平联合使用在一组中使血压下降13±3/13±3（均值±标准差）mmHg，在另一组中使血压下降14±3/14±2（均值±标准差）mmHg。停用喹那普利6周后，单独使用氨氯地平未引起血压变化（0±3/-2±3）（均值±标准差）。无论治疗如何，在第2次访视与第1次访视以及第3次访视与第2次访视时，MSNA每100次心跳减少3次爆发（时间效应P = 0.02）。在第一组中，每次访视时血管紧张素II略有增加，在第二组中略有下降（治疗效应P = 0.02）。
氨氯地平似乎不会激活肾素-血管紧张素系统来抵消其在年轻高血压患者中的降压作用。同样，在基线时或由氨氯地平诱导时，MSNA中似乎不存在血管紧张素II依赖性成分。
