Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy

Larissa B. Teixeira, Lucas T. Parreiras-E-Silva, Thiago Bruder-Nascimento, Diego A. Duarte, Sarah C. Simões, Rafael M. Costa, Deisy Y. Rodríguez, Pedro A.B. Ferreira, Carlos A.A. Silva, Emiliana P. Abrao, Eduardo B. Oliveira, Michel Bouvier, Rita C. Tostes, Claudio M. Costa-Neto

Producción científica: Artículos / NotasArtículo Científicorevisión exhaustiva

89 Citas (Scopus)

Resumen

The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R. Here we show that Ang-(1-7) binds to the AT1R without activating Gq, but triggering β-arrestins 1 and 2 recruitment and activation. Using an in vivo model of cardiac hypertrophy, we show that Ang-(1-7) significantly attenuates heart hypertrophy by reducing both heart weight and ventricular wall thickness and the increased end-diastolic pressure. Whereas neither the single blockade of AT1 or Mas receptors with their respective antagonists prevented the cardioprotective action of Ang1-7, combination of the two antagonists partially impaired the effect of Ang-(1-7). Taken together, these data indicate that Ang-(1-7) mediates at least part of its cardioprotective effects by acting as an endogenous β-arrestin-biased agonist at the AT1R.

Idioma originalInglés
Número de artículo11903
PublicaciónScientific reports
Volumen7
N.º1
DOI
EstadoPublicada - 1 dic. 2017
Publicado de forma externa

Huella

Profundice en los temas de investigación de 'Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy'. En conjunto forman una huella única.

Citar esto