title: Long-term ouabain treatment impairs vascular function in resistance arteries.
abstract: OBJECTIVE
  The purpose of this study was to examine the cardiovascular effects of long-term ouabain treatment at different time points.
  
  
  METHODS
  Systolic blood pressure (SBP) was measured by tail-cuff method in male Wistar rats treated with ouabain (approx. 8.0 μg·day(-1)) or vehicle for 5, 10 and 20 weeks. Afterwards, vascular function was assessed in mesenteric resistance arteries (MRA) using a wire myograph. ROS production and COX-1 and COX-2, TNF-α, and IL-6 protein expression were investigated.
  
  
  RESULTS
  SBP was increased by ouabain treatment up to the 6th week and remained stable until the 20th week. However, noradrenaline-induced contraction increased only in MRA in rats treated with ouabain for 20 weeks. NOS inhibition and endothelium removal increased the noradrenaline response, but to a smaller magnitude in MRA in the ouabain group. Moreover, inhibition of COX-2 or incubation with superoxide dismutase restores noradrenaline-induced contraction in the 20-week ouabain group to control levels. ROS production as well as COX-2, IL-6 and TNF-α protein expression increased in MRA in this group.
  
  
  CONCLUSIONS
  Although ouabain treatment induced hypertension in all groups, a larger noradrenaline induced contraction was observed over 20 weeks of treatment. This vascular dysfunction was related to COX-2-derived prostanoids and oxidative stress, increased pro- inflammatory cytokines and reduced NO bioavailability.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Camilla Ferreira
authors.initials: CF
authors.lastname: Wenceslau
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Davel
authors.forename: Fabiano Elias
authors.initials: FE
authors.lastname: Xavier
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010042:Ouabain / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D010042:Ouabain; D051546:Cyclooxygenase 2