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多沙唑嗪和依那普利对睡眠呼吸暂停患者周围血管紧张度和夜间血压的双盲、交叉研究。

A double-blind, crossover study of Doxazosin and Enalapril on peripheral vascular tone and nocturnal blood pressure in sleep apnea patients.

机构信息

Sleep Laboratory, Department of Pulmonary Medicine, Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden.

出版信息

Sleep Med. 2010 Mar;11(3):325-8. doi: 10.1016/j.sleep.2009.10.004. Epub 2010 Feb 18.

Abstract

OBJECTIVE

Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral alpha-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients.

METHODS

A double-blind, crossover study comparing equipotent dosages of DO (4 mg/day for 2 weeks with 8 mg/day for an additional 2 weeks) and EN (10mg/day and 20mg/day, respectively) was undertaken in 16 male OSA patients (age 55+/-7 years, body mass index 30.1+/-3.8 kg/m(2)) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed.

RESULTS

There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129+/-13 vs. 119+/-23 mm Hg, P=0.02; diastolic BP 81+/-12 vs. 74+/-14 mm Hg, P=0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P<0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P<0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P=0.002).

CONCLUSION

Digital vasoconstrictions associated with apneic events are alpha-receptor mediated. DO compared to EN has a proportionally poor effect on nocturnal BP control in OSA patients, which may be due to the enhanced sympathetic nervous system activity characteristic of this condition.

摘要

目的

与阻塞性睡眠呼吸暂停(OSA)相关的脉搏波衰减是交感神经介导的。我们比较了多沙唑嗪(DO,外周α受体抑制剂)和依那普利(EN,ACE 抑制剂)对高血压 OSA 患者的数字血管收缩和夜间血压(BP)的影响。

方法

在 16 名患有高血压的男性 OSA 患者(年龄 55+/-7 岁,体重指数 30.1+/-3.8kg/m²)中进行了一项双盲、交叉研究,比较了等效剂量的 DO(4mg/天,持续 2 周,然后增加 8mg/天,持续 2 周)和 EN(分别为 10mg/天和 20mg/天)。在每个治疗期结束时进行包括动态 24 小时血压、全夜多导睡眠图伴同时外周动脉张力(PAT)和逐搏手指血压监测(Finapres)的评估。分析与呼吸暂停事件相关的夜间血压和数字血管收缩(通过测量呼吸暂停期间和之后的 PAT 幅度比来衡量)。

结果

两种治疗方法在 24 小时血压谱和 OSA 严重程度方面没有差异。但是,DO 治疗下夜间平均逐搏手指血压明显升高(收缩压 129+/-13 与 119+/-23mmHg,P=0.02;舒张压 81+/-12 与 74+/-14mmHg,P=0.04,分别为 DO 和 EN)。在线性混合效应回归模型中,与 EN 相比,DO 下呼吸暂停期间的 PAT 比值增加了 5.3%(P<0.0001)。每减少 1%与呼吸暂停相关的氧去饱和,PAT 比值就会降低 0.9%(P<0.0001)。与 NREM 睡眠相比,REM 睡眠使 PAT 比值降低 2.2%(P=0.002)。

结论

与呼吸暂停事件相关的数字血管收缩是由α受体介导的。与 EN 相比,DO 对 OSA 患者的夜间血压控制效果较差,这可能是由于这种情况下交感神经系统活动增强所致。

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