title: Circulating anandamide and blood pressure in patients with obstructive sleep apnea.
abstract: OBJECTIVE
  Obstructive sleep apnea chronically increases blood pressure through sympathetic nervous system activation. In animals, hypertension and sympathetic activity are restrained by cannabinoid receptor activation. Therefore, we hypothesized that increased blood pressure in patients with obstructive sleep apnea is associated with increased circulating endocannabinoid concentrations.
  
  
  METHODS
  Arterial oxygen saturation and apnea/hypopnea episodes were recorded in 29 patients with normal glucose tolerance, 26 patients with type 2 diabetes mellitus, and 21 patients obese subjects without sleep apnea. We determined seated blood pressure, insulin, glucose, and high-sensitive C-reactive protein in the morning, and insulin sensitivity by euglycemic-hyperinsulinemic clamp the next day. Anandamide, the sum of 1-arachidonoylglycerol and 2-arachidonoylglycerol, and oleoylethanolamide were measured in plasma by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Endocannabinoid concentrations in sleep apnea patients were increased compared to obese individuals without disordered nocturnal breathing. Correction for variables of obesity and insulin resistance almost completely abrogated this difference in endocannabinoids. Anandamide strongly correlated with blood pressure in sleep apnea patients (r = 0.60 for SBP and r = 0.58 for DBP, P < 0.001). In multivariate regression analysis, anandamide was a stronger determinant of blood pressure than sleep apnea severity, obesity, insulin resistance, and inflammation.
  
  
  CONCLUSIONS
  Obstructive sleep apnea patients show positive correlations between blood pressure and venous anandamide concentrations independent of confounding factors. Our data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.
authors.affiliation: Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany. engeli.stefan@mh-hannover.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Reiner
authors.initials: R
authors.lastname: Jumpertz
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiesner
authors.forename: Hubertus
authors.initials: H
authors.lastname: Wirtz
authors.forename: Andrea
authors.initials: A
authors.lastname: Bosse-Henck
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Sandor
authors.initials: S
authors.lastname: Batkai
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.forename: Judy
authors.initials: J
authors.lastname: Harvey-White
authors.forename: George
authors.initials: G
authors.lastname: Kunos
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000368:Aged; D001095:Arachidonic Acids / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D053284:Polyunsaturated Alkamides / Q000097:blood*; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000503:physiopathology*
chemical_list: D001095:Arachidonic Acids; D015415:Biomarkers; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide