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

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 α-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 (4mg/day for 2weeks with 8mg/day for an additional 2weeks) and EN (10mg/day and 20mg/day, respectively) was undertaken in 16 male OSA patients (age 55±7years, body mass index 30.1±3.8kg/m²) 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±23mm Hg, P=0.02; diastolic BP 81±12 vs. 74±14mm 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 α-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.

Keywords: Antihypertensive treatment, Autonomic nervous system, Blood pressure, Obstructive sleep apnea, Peripheral arterial tone, Pulse wave attenuation