title: Ouabain induces nitric oxide release by a PI3K/Akt-dependent pathway in isolated aortic rings from rats with heart failure.
abstract: BACKGROUND
  Ouabain occurs in nanomolar concentrations in myocardial infarction and heart failure (HF). However, the effects of ouabain in vascular function in HF conditions were not investigated yet. Therefore, we analyzed the effects of acute administration of 3 nM ouabain in isolated aortic rings from rats with HF 4 weeks after myocardial infarction.
  
  
  RESULTS
  Rats were submitted to sham operation or coronary artery occlusion. In HF rats, left ventricular positive and negative derivatives of intraventricular pressure reduced and left ventricular end diastolic pressure increased. Phenylephrine responses increased in HF rings when compared with controls. Ouabain incubation for 45 minutes reduced phenylephrine-induced contraction in both groups. Endothelial removal increased more phenylephrine response in ouabain-treated rings of sham rats. Ouabain potentiated the effect of L-NAME in both groups but more in sham rats. Wortmannin increased the phenylephrine response only in HF rings. The effect of tetraethylammonium was potentiated by ouabain only in HF rings. Ouabain increased phenylephrine-stimulated nitric oxide production in rings from both groups but increased the activation of Akt only in vessels from HF rats.
  
  
  CONCLUSIONS
  Results demonstrate that low ouabain concentration can decrease vascular reactivity of aortic rings from HF rats. Ouabain was able to increase nitric oxide production in HF rats by triggering a signal transduction PI3K/Akt-dependent pathway and increasing an endothelium-hyperpolarizing factor release.
authors.affiliation: *Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil; and †Department of Physiological Sciences, EMESCAM, Vitoria, Brazil.
authors.forename: Fabiana D M
authors.initials: FD
authors.lastname: Siman
authors.forename: Edna A
authors.initials: EA
authors.lastname: Silveira
authors.forename: Aurélia A
authors.initials: AA
authors.lastname: Fernandes
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Padilha
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010042:Ouabain / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010656:Phenylephrine; D009569:Nitric Oxide; D010042:Ouabain; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019331:NG-Nitroarginine Methyl Ester