title: Cyclo-oxygenase-2 knockout genotype in mice is associated with blunted angiotensin II-induced oxidative stress and hypertension.
abstract: BACKGROUND
  Inflammation and oxidative stress have been identified as integral parts in the pathogenesis of hypertension. Cyclo-oxygenase-2 which could elicit inflammation and free radicals generation appears to be a key enzyme in hypertension. Cyclo-oxygenase-2 expression and oxidative stress in cardiovascular tissues are increased in the angiotensin II model.
  
  
  METHODS
  Cyclo-oxygenase-1 and cyclo-oxygenase-2 deficient mice and their cultured aortic smooth muscle cells were used to investigate the role of these enzymes in angiotensin II induced superoxide production and hypertension.
  
  
  RESULTS
  At resting state, the superoxide production in aortic and cardiac tissues was lower in cyclo-oxygenase-2 deficient than in the wild type or in cyclo-oxygenase-1 deficient mice. Chronic angiotensin II infusion increased the superoxide production in these tissues from both cyclo-oxygenase-deficient and wild-type mice whereas the level in cyclo-oxygenase-2 deficient mice was equivalent to the basal level in wild-type mice. The hypertensive effect of angiotensin II was attenuated in cyclo-oxygenase-2 deficient mice. Aspirin treatment reduced the basal superoxide production and blunted the oxidative and hypertensive effect of angiotensin II in wild type and cyclo-oxygenase-1 deficient mice whereas it lost completely its antioxidative property in angiotensin II-treated aortic smooth muscle cells isolated from cyclo-oxygenase-2 deficient mice.
  
  
  CONCLUSIONS
  Cyclo-oxygenase-2 pathway plays a major role in the superoxide generation as well as in the angiotensin II-induced oxidative stress and blood pressure. Cyclo-oxygenase-1 activity didn't show any influence on these parameters. These results suggest that cyclo-oxygenase-2 is involved in the pathogenesis of hypertension.
authors.affiliation: Department of Pharmacology, Université de Montréal, Quebec, Canada.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Sonia
authors.initials: S
authors.lastname: Duchemin
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Laplante
authors.forename: Jacques
authors.initials: J
authors.lastname: De Champlain
authors.forename: Helene
authors.initials: H
authors.lastname: Girouard
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000172:deficiency; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D000804:Angiotensin II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D001241:Aspirin