Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

dc.creatorGazzoto, A
dc.creatorKinote, A
dc.creatorPereira, DJ
dc.creatorRenno, A
dc.creatordos Santos, RC
dc.creatorFerreira-Melo, SE
dc.creatorVelloso, LA
dc.creatorBordin, S
dc.creatorAnhe, GF
dc.creatorMoreno, H
dc.date2013
dc.date10959
dc.date2014-07-30T14:33:28Z
dc.date2015-11-26T16:33:17Z
dc.date2014-07-30T14:33:28Z
dc.date2015-11-26T16:33:17Z
dc.date.accessioned2018-03-28T23:15:05Z
dc.date.available2018-03-28T23:15:05Z
dc.identifierEuropean Journal Of Pharmacology. Elsevier Science Bv, v. 700, n. 41699, n. 201, n. 209, 2013.
dc.identifier0014-2999
dc.identifier1879-0712
dc.identifierWOS:000315160600026
dc.identifier10.1016/j.ejphar.2012.11.059
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60171
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60171
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1270802
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionHigh systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threoninekinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-alpha (TNF alpha) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNF alpha-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-kappa B (I kappa beta) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. (C) 2012 Elsevier B.V. All rights reserved.
dc.description700
dc.description41699
dc.description201
dc.description209
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageen
dc.publisherElsevier Science Bv
dc.publisherAmsterdam
dc.publisherHolanda
dc.relationEuropean Journal Of Pharmacology
dc.relationEur. J. Pharmacol.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectInfliximab
dc.subjectHypertension
dc.subjectInsulin resistance
dc.subjectTNF alpha
dc.subjecteNOS
dc.subjectNecrosis-factor-alpha
dc.subjectNitric-oxide Synthase
dc.subjectInsulin-signaling Pathways
dc.subjectNf-kappa-b
dc.subjectEndothelial-cells
dc.subjectTyrosine Phosphorylation
dc.subjectMetabolic Syndrome
dc.subjectTnf-alpha
dc.subjectResistance
dc.subjectReceptor
dc.titleInfliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats
dc.typeArtículos de revistas


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