title: Increased vascular contractility and oxidative stress in β₂-adrenoceptor knockout mice: the role of NADPH oxidase.
abstract: OBJECTIVE
  β(2)-adrenoceptor (β(2)-AR) activation induces smooth muscle relaxation and endothelium-derived nitric oxide (NO) release. However, whether endogenous basal β(2)-AR activity controls vascular redox status and NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in mice lacking functional β(2)-AR (β(2)KO), focusing on the role of NO and superoxide anion.
  
  
  RESULTS
  Isolated thoracic aortas from β(2)KO and wild-type mice (WT) were studied. β(2)KO aortas exhibited an enhanced contractile response to phenylephrine compared to WT. Endothelial removal and L-NAME incubation increased phenylephrine-induced contraction, abolishing the differences between β(2)KO and WT mice. Basal NO availability was reduced in aortas from β(2)KO mice. Incubation of β(2)KO aortas with superoxide dismutase or NADPH inhibitor apocynin restored the enhanced contractile response to phenylephrine to WT levels. β(2)KO aortas exhibited oxidative stress detected by enhanced dihydroethidium fluorescence, which was normalized by apocynin. Protein expression of eNOS was reduced, while p47(phox) expression was enhanced in β(2)KO aortas.
  
  
  CONCLUSIONS
  The present results demonstrate for the first time that enhanced NADPH-derived superoxide anion production is associated with reduced NO bioavailability in aortas of β(2)KO mice. This study extends the knowledge of the relevance of the endogenous activity of β(2)-AR to the maintenance of the vascular physiology.
authors.affiliation: Department of Anatomy, Institute of Biology, State University of Campinas-UNICAMP, Campinas, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Davel
authors.forename: G S
authors.initials: GS
authors.lastname: Ceravolo
authors.forename: C F
authors.initials: CF
authors.lastname: Wenceslau
authors.forename: M H C
authors.initials: MH
authors.lastname: Carvalho
authors.forename: P C
authors.initials: PC
authors.lastname: Brum
authors.forename: L V
authors.initials: LV
authors.lastname: Rossoni
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D018384:Oxidative Stress; D010656:Phenylephrine / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000172:deficiency*; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000098:Acetophenones; D018343:Receptors, Adrenergic, beta-2; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; C056165:acetovanillone; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1