title: Microvascular endothelial dysfunction in obstructive sleep apnea is caused by oxidative stress and improved by continuous positive airway pressure therapy.
abstract: BACKGROUND
  Endothelial dysfunction has recently been demonstrated in obstructive sleep apnea (OSA), but the underlying mechanisms are not entirely understood. Oxidative stress is a typical feature of OSA.
  
  
  OBJECTIVE
  We investigated the influence of oxidative stress and continuous positive airway pressure (CPAP) on microvascular endothelial function in OSA.
  
  
  METHODS
  Endothelial function of forearm resistance vessels was assessed by strain gauge venous occlusion plethysmography after intra-arterial infusion of the endothelium-independent vasodilator sodium nitroprusside (1.6, 3.2, and 4.0 μg/min) and the endothelium-dependent vasodilator acetylcholine (Ach, 15, 30 and 40 μg/min) in patients with (n = 11) and without (n = 8) OSA (apnea-hypopnea index ≥15/h). These measurements have been repeated after local intra-arterial infusion of the antioxidant vitamin C (25 μg/min). Furthermore, 6 patients have been reevaluated after 6 months of OSA treatment.
  
  
  RESULTS
  Patients with OSA demonstrated impaired endothelial function compared to those without OSA. Thus, related to baseline flow, the increase in forearm blood flow induced by Ach was blunted in patients with OSA (148.7 ± 29.7% in OSA vs. 233.6 ± 45.7% in controls, p = 0.001). This difference, however, was abolished by co-infusion of vitamin C. Endothelial function markedly improved following treatment in 5 of 6 OSA patients.
  
  
  CONCLUSIONS
  This study strongly suggests that microvascular endothelial function is affected by OSA predominantly through increased oxidative stress, and treatment of OSA may improve endothelial function mainly by reducing oxidative stress. The role of oxidative stress-induced endothelial dysfunction as a potential promoter of atherosclerosis and an increased cardiovascular risk in patients with OSA should be investigated in further controlled studies.
authors.affiliation: Department of Internal Medicine I, Marienhospital Herne, Ruhr-University Bochum, Herne, Germany.
authors.forename: Nikolaus J
authors.initials: NJ
authors.lastname: Büchner
authors.forename: Ivo
authors.initials: I
authors.lastname: Quack
authors.forename: Magdalena
authors.initials: M
authors.lastname: Woznowski
authors.forename: Constanze
authors.initials: C
authors.lastname: Stähle
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wenzel
authors.forename: Lars C
authors.initials: LC
authors.lastname: Rump
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D050197:Atherosclerosis / Q000503:physiopathology; D001783:Blood Flow Velocity; D002196:Capillaries / Q000503:physiopathology; D045422:Continuous Positive Airway Pressure; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage; D018384:Oxidative Stress; D010991:Plethysmography; D017286:Polysomnography; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D001205:Ascorbic Acid