Angiotensin-converting enzyme 2 activation improves endothelial function

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dc.creatorSilva, Rodrigo Araújo Fraga da
dc.creatorFraga, Fabiana Pereira da Costa
dc.creatorMurça, Tatiane Moisés
dc.creatorMoraes, Patrícia L.
dc.creatorLima, Augusto Martins
dc.creatorLautner, Roberto Queiroga
dc.creatorCastro, Carlos Henrique
dc.creatorSoares, Célia Maria de Almeida
dc.creatorBorges, Clayton Luiz
dc.creatorNadu, Ana Paula
dc.creatorOliveira, Marilene Luzia de
dc.creatorShenoy, Vinayak
dc.creatorKatovich, Michael J.
dc.creatorSantos, Robson A. S.
dc.creatorRaizada, Mohan K.
dc.creatorFerreira, Anderson José
dc.date.accessioned2018-08-22T13:04:07Z
dc.date.available2018-08-22T13:04:07Z
dc.date.issued2013-06
dc.description.abstractDiminished release and function of endothelium-derived nitric oxide coupled with increases in reactive oxygen species production is critical in endothelial dysfunction. Recent evidences have shown that activation of the protective axis of the renin–angiotensin system composed by angiotensin-converting enzyme 2, angiotensin-(1–7), and Mas receptor promotes many beneficial vascular effects. This has led us to postulate that activation of intrinsic angiotensin-converting enzyme 2 would improve endothelial function by decreasing the reactive oxygen species production. In the present study, we tested 1-[[2-(dimetilamino)etil]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT), a small molecule angiotensin-converting enzyme 2 activator, on endothelial function to validate this hypothesis. In vivo treatment with XNT (1 mg/kg per day for 4 weeks) improved the endothelial function of spontaneously hypertensive rats and of streptozotocin-induced diabetic rats when evaluated through the vasorelaxant responses to acetylcholine/ sodium nitroprusside. Acute in vitro incubation with XNT caused endothelial-dependent vasorelaxation in aortic rings of rats. This vasorelaxation effect was attenuated by the Mas antagonist D-pro7-Ang-(1–7), and it was reduced in Mas knockout mice. These effects were associated with reduction in reactive oxygen species production. In addition, Ang II–induced reactive oxygen species production in human aortic endothelial cells was attenuated by preincubation with XNT. These results showed that chronic XNT administration improves the endothelial function of hypertensive and diabetic rat vessels by attenuation of the oxidative stress. Moreover, XNT elicits an endothelial-dependent vasorelaxation response, which was mediated by Mas. Thus, this study indicated that angiotensin-converting enzyme 2 activation promotes beneficial effects on the endothelial function and it is a potential target for treating cardiovascular disease.pt_BR
dc.identifier.citationFRAGA-SILVA, Rodrigo A.; COSTA-FRAGA, Fabiana P.; MURCA, Tatiane M.; MORAES, Patrícia L.; MARTINS, Augusto Martins; LAUTNER, Roberto Q.; CASTRO, Carlos H.; SOARES, Célia Maria A.; BORGES, Clayton L.; NADU, Ana Paula; OLIVEIRA, Marilene L.; SHENOY, Vinayak; KATOVICH, Michael J.; SANTOS, Robson A. S.; RAIZADA, Mohan K.; FERREIRA, Anderson J. Angiotensin-converting enzyme 2 activation improves endothelial function. Hypertension, Dallas, v. 61, n. 6, p. 1233-1238, June 2013.pt_BR
dc.identifier.doi 10.1161/HYPERTENSIONAHA.111.00627
dc.identifier.issn0194-911X
dc.identifier.issne- 1524-4563
dc.identifier.urihttp://repositorio.bc.ufg.br/handle/ri/15690
dc.language.isoengpt_BR
dc.publisher.countryEstados unidospt_BR
dc.publisher.departmentInstituto de Ciências Biológicas - ICB (RG)pt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectAngiotensin-(1 – 7)pt_BR
dc.subjectDiabetes mellituspt_BR
dc.subjectEndothelium dysfunctionpt_BR
dc.subjectOxidative stresspt_BR
dc.subjectRenin – angiotensin systempt_BR
dc.titleAngiotensin-converting enzyme 2 activation improves endothelial functionpt_BR
dc.typeArtigopt_BR

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