Original ArticleOuabain Induces Nitric Oxide Release by a PI3K/Akt-dependent Pathway in Isolated Aortic Rings From Rats With Heart FailureSiman, Fabiana D. M. PhD*; Silveira, Edna A. PhD*; Fernandes, Aurélia A. PhD*; Stefanon, Ivanita PhD*; Vassallo, Dalton V. PhD*,†; Padilha, Alessandra S. PhD*Author Information *Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Brazil; and †Department of Physiological Sciences, EMESCAM, Vitoria, Brazil. Reprints: Alessandra S. Padilha, PhD, Department of Physiological Sciences, Federal University of Espirito Santo, Av. Marechal Campos, 1468, Maruípe, 29043-090 Vitoria, ES, Brazil (e-mail: firstname.lastname@example.org). Supported by grants from CNPq, CAPES, and FAPES/FUNCITEC. The authors report no conflicts of interest. Received March 10, 2014 Accepted August 01, 2014 Journal of Cardiovascular Pharmacology: January 2015 - Volume 65 - Issue 1 - p 28-38 doi: 10.1097/FJC.0000000000000160 Buy Metrics 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. Methods and 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. © 2015 by Lippincott Williams & Wilkins.