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


CONCLUSIONS
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.
Zou
Ding
D
Sleep Laboratory, Department of Pulmonary Medicine, Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden. zou.ding@lungall.gu.se
Grote
Ludger
L
Eder
Derek N
DN
Radlinski
Jakub
J
Hedner
Jan
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017292:Doxazosin / Q000494:pharmacology / Q000627:therapeutic use*; D004656:Enalapril / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000187:drug effects; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D004656:Enalapril; D017292:Doxazosin