title: Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH.
  
  
  RESULTS
  Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02).
  
  
  CONCLUSIONS
  COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA.
  
  
  BACKGROUND
  www.clinicaltrials.gov. Unique identifier: NCT01280006.
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Beaudin
authors.forename: Matiram
authors.initials: M
authors.lastname: Pun
authors.forename: Christina
authors.initials: C
authors.lastname: Yang
authors.forename: David D M
authors.initials: DD
authors.lastname: Nicholl
authors.forename: Craig D
authors.initials: CD
authors.lastname: Steinback
authors.forename: Donna M
authors.initials: DM
authors.lastname: Slater
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Wynne-Edwards
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanly
authors.forename: Sofia B
authors.initials: SB
authors.lastname: Ahmed
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Poulin
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D000068579:Celecoxib; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000652:urine; D015232:Dinoprostone / Q000652:urine; D004311:Double-Blind Method; D011464:Epoprostenol / Q000652:urine; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000494:pharmacology; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000652:urine
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D013928:Thromboxane A2; D015237:Dinoprost; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin
keywords: blood pressure; cerebrovascular circulation; intermittent hypoxia; obstructive sleep apnea; prostaglandins