title: Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea.
abstract: Obstructive sleep apnea (OSA) is characterized by noradrenergic activation. Nasal continuous positive airway pressure (CPAP) is the treatment of choice and has been shown to effectively reduce elevated norepinephrine (NE) levels. This study examined whether the reduction in NE after CPAP is due to an increase in NE clearance and/or a decrease of NE release rate. Fifty CPAP-naive OSA patients with an apnea-hypopnea index >15 were studied. NE clearance and release rates, circulating NE levels, urinary NE excretion, and blood pressure and heart rate were determined before and after 14 days of CPAP, placebo CPAP (CPAP administered at ineffective pressure), or oxygen supplementation. CPAP led to a significant increase in NE clearance (P < or = 0.01), as well as decreases in plasma NE levels (P < or = 0.018) and daytime (P < 0.001) and nighttime (P < 0.05) NE excretion. NE release rate was unchanged with treatment. Systolic (P < or = 0.013) and diastolic (P < or = 0.026) blood pressure and heart rate (P < or = 0.014) were decreased in response to CPAP but not in response to oxygen or placebo CPAP treatment. Posttreatment systolic blood pressure was best predicted by pretreatment systolic blood pressure and posttreatment NE clearance and release rate (P < 0.01). The findings indicate that one of the mechanisms through which CPAP reduces NE levels is through an increase in the clearance of NE from the circulation.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. pmills@ucsd.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mills
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kennedy
authors.forename: Jose S
authors.initials: JS
authors.lastname: Loredo
authors.forename: Joel E
authors.initials: JE
authors.lastname: Dimsdale
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ziegler
mesh_terms: D000328:Adult; D000818:Animals; D001794:Blood Pressure; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D004734:Energy Metabolism; D005260:Female; D006339:Heart Rate; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D010100:Oxygen / Q000008:administration & dosage*; D016037:Single-Blind Method; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D010100:Oxygen; D009638:Norepinephrine