Upregulation of ERK1/2-eNOS via AT2 Receptors Decreases the Contractile Response to Angiotensin II in Resistance Mesenteric Arteries from Obese Rats

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dc.contributor.authorHagihara, Graziela N.
dc.contributor.authorLobato, Nubia S.
dc.contributor.authorFilgueira, Fernando P.
dc.contributor.authorAkamine, Eliana H.
dc.contributor.authorAragao, Danielle S. [UNIFESP]
dc.contributor.authorCasarini, Dulce Elena [UNIFESP]
dc.contributor.authorCarvalho, Maria Helena C.
dc.contributor.authorFortes, Zuleica B.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de Goiás (UFG)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:37:44Z
dc.date.available2016-01-24T14:37:44Z
dc.date.issued2014-08-29
dc.description.abstractIt has been clearly established that mitogen-activated protein kinases (MAPKS) are important mediators of angiotensin II (Ang II) signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. the role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese) and non-obese Wistar rats (control) were used. the circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS) or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats.en
dc.description.affiliationUniv São Paulo, Inst Biomed Sci, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUniv Fed Goias, Div Cardiovasc Physiol, Dept Biol Sci, Jatai, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Div Nephrol, Dept Med, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Nephrol, Dept Med, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIDFAPESP: 2007/58311-0
dc.description.sponsorshipIDFAPESP: 2008/51622-3
dc.description.sponsorshipIDFAPESP: 2010/03642-5
dc.format.extent10
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0106029
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 9, n. 8, 10 p., 2014.
dc.identifier.doi10.1371/journal.pone.0106029
dc.identifier.fileWOS000341127500090.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38107
dc.identifier.wosWOS:000341127500090
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleUpregulation of ERK1/2-eNOS via AT2 Receptors Decreases the Contractile Response to Angiotensin II in Resistance Mesenteric Arteries from Obese Ratsen
dc.typeinfo:eu-repo/semantics/article
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