Use este identificador para citar ou linkar para este item: http://repositorio.bc.ufg.br/handle/ri/15690
Tipo do documento: Artigo
Título: Angiotensin-converting enzyme 2 activation improves endothelial function
Autor: Silva, Rodrigo Araújo Fraga da
Fraga, Fabiana Pereira da Costa
Murça, Tatiane Moisés
Moraes, Patrícia L.
Lima, Augusto Martins
Lautner, Roberto Queiroga
Castro, Carlos Henrique
Soares, Célia Maria de Almeida
Borges, Clayton Luiz
Nadu, Ana Paula
Oliveira, Marilene Luzia de
Shenoy, Vinayak
Katovich, Michael J.
Santos, Robson A. S.
Raizada, Mohan K.
Ferreira, Anderson José
Abstract: Diminished 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.
Palavras-chave: Angiotensin-(1 – 7)
Diabetes mellitus
Endothelium dysfunction
Oxidative stress
Renin – angiotensin system
País: Estados unidos
Unidade acadêmica: Instituto de Ciências Biológicas - ICB (RG)
Citação: FRAGA-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.
Tipo de acesso: Acesso Aberto
Identificador do documento:  10.1161/HYPERTENSIONAHA.111.00627
Identificador do documento:  10.1161/HYPERTENSIONAHA.111.00627
URI: http://repositorio.bc.ufg.br/handle/ri/15690
Data de publicação: Jun-2013
Aparece nas coleções:ICB - Artigos publicados em periódicos

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