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褪黑素对硝苯地平控制良好的高血压患者的心血管效应:一项24小时研究。

Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study.

作者信息

Lusardi P, Piazza E, Fogari R

机构信息

Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.

出版信息

Br J Clin Pharmacol. 2000 May;49(5):423-7. doi: 10.1046/j.1365-2125.2000.00195.x.

DOI:10.1046/j.1365-2125.2000.00195.x
PMID:10792199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2014953/
Abstract

AIMS

As melatonin has been found to play a role in the mechanisms of cardiovascular regulation, we designed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy.

METHODS

Forty-seven mild to moderate essential hypertensive outpatients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months, were given placebo or melatonin 5 mg at 22.30 h for 4 weeks according to a double-blind cross-over study. At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring (ABPM) during usual working days; sleeping period was scheduled to last from 23.00 to 07.00 h.

RESULTS

The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period (DeltaSBP = + 6.5 mmHg, P < 0.001; DeltaDBP = + 4.9 mmHg, P < 0.01; DeltaHR = + 3.9 beats min-1, P < 0.01). The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours.

CONCLUSIONS

We hypothesize that competition between melatonin and nifedipine, is able to impair the antihypertensive efficacy of the calcium channel blocker. This suggests caution in uncontrolled use of melatonin in hypertensive patients. As the pineal hormone might interfere with calcium channel blocker therapy, it cannot be considered simply a dietary supplement.

摘要

目的

由于已发现褪黑素在心血管调节机制中发挥作用,我们设计了本研究,以评估晚间摄入这种松果体激素是否会干扰硝苯地平单药治疗控制良好的高血压患者的抗高血压治疗。

方法

47例轻度至中度原发性高血压门诊患者,于08:30服用硝苯地平控释片30或60mg单药治疗至少3个月,根据双盲交叉研究,于22:30给予安慰剂或5mg褪黑素,持续4周。在每个治疗期结束时,患者在正常工作日接受24小时无创动态血压监测(ABPM);睡眠时间安排为从23:00至07:00。

结果

晚间服用褪黑素导致24小时内血压和心率升高(收缩压变化量=+6.5mmHg,P<0.001;舒张压变化量=+4.9mmHg,P<0.01;心率变化量=+3.9次/分钟,P<0.01)。舒张压和心率升高在上午和下午时段尤为明显。

结论

我们推测褪黑素与硝苯地平之间的竞争能够削弱钙通道阻滞剂的抗高血压疗效。这表明高血压患者在无节制使用褪黑素时应谨慎。由于松果体激素可能会干扰钙通道阻滞剂治疗,因此不能简单地将其视为一种膳食补充剂。

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本文引用的文献

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Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects.睡前摄入褪黑素对血压正常受试者血压的影响。
Blood Press Monit. 1997 Apr;2(2):99-103.
2
Impaired basal sympathetic tone and alpha1-adrenergic responsiveness in association with the hypotensive effect of melatonin in spontaneously hypertensive rats.自发性高血压大鼠中,基础交感神经张力和α1肾上腺素能反应性受损与褪黑素的降压作用相关。
Am J Hypertens. 1998 Feb;11(2):219-29. doi: 10.1016/s0895-7061(97)00401-9.
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Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine: role of pharmacokinetics.硝苯地平对心脏和外周交感神经系统的差异性激活作用:药代动力学的作用
J Am Coll Cardiol. 1997 Jun;29(7):1607-14. doi: 10.1016/s0735-1097(97)00095-8.
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[Effects of melatonin on muscle contractility and neuromuscular blockade produced by muscle relaxants].
Masui. 1997 Feb;46(2):205-12.
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Melatonin in humans.人体内的褪黑素。
N Engl J Med. 1997 Jan 16;336(3):186-95. doi: 10.1056/NEJM199701163360306.
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The Mel1a melatonin receptor is coupled to parallel signal transduction pathways.Mel1a褪黑素受体与平行信号转导途径偶联。
Endocrinology. 1997 Jan;138(1):397-404. doi: 10.1210/endo.138.1.4824.
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Melatonin potentially useful but safety, efficacy remain uncertain.褪黑素可能有用,但安全性和有效性仍不确定。
JAMA. 1996 Oct 2;276(13):1011-4.
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Melatonin efficacy in aviation missions requiring rapid deployment and night operations.褪黑素在需要快速部署和夜间行动的航空任务中的功效。
Aviat Space Environ Med. 1996 Jun;67(6):520-4.
9
Does melatonin affect calcium influx in human aortic smooth muscle cells and estradiol-mediated calcium antagonism?褪黑素是否会影响人主动脉平滑肌细胞中的钙内流以及雌二醇介导的钙拮抗作用?
J Pineal Res. 1996 Apr;20(3):145-7. doi: 10.1111/j.1600-079x.1996.tb00250.x.
10
In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin.褪黑素对体外Ca2+/钙调蛋白依赖性激酶II活性的抑制作用
Biochim Biophys Acta. 1996 Jun 4;1290(2):191-6. doi: 10.1016/0304-4165(96)00025-6.