IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Angiotensin (ANG)-(1-7) elicits a dualrole on growth-promoting signaling pathways in rat heart in vivo by stimulating STAT3 and 5a/b phosphorylation and inhibiting ANG II-stimulated ERK1/2 and Rho-kinase activity.
Autor/es:
GIANI JF; GIRONACCI MM; MUÑOZ MC; TURYN D; DOMINICI FP
Revista:
EXPERIMENTAL PHYSIOLOGY.
Editorial:
Blackwell Publishing
Referencias:
Año: 2008 vol. 93 p. 570 - 578
ISSN:
0958-0670
Resumen:
Angiotensin (ANG) II contributes to cardiac remodelling by inducing the activation of several signalling molecules, including ERK1/2, Rho kinase and members of the STAT family of proteins. Angiotensin-(17) is produced in the heart and inhibits the proliferative actions of ANG II, although the mechanisms of this inhibition are poorly understood. Accordingly, in the present study we examined whether ANG-(17) affects the ANG II-mediated activation of ERK1/2 and Rho kinase, STAT3 and STAT5a/b in rat heart in vivo. We hypothesized that ANG-(17) inhibits these growth-promoting pathways, counterbalancing the trophic action of ANG II. Solutions of normal saline (0.9% NaCl) containing ANG II (8 pmol kg1) plus ANG-(17) in increasing doses (from 0.08 to 800 pmol kg1) were administered via the inferior vena cava to anaesthetized male SpragueDawley rats. After 5 min, hearts were removed and ERK1/2, Rho kinase, STAT3 and STAT5a/b phosphorylation was determined by Western blotting using phosphospecific antibodies. Angiotensin II stimulated ERK1/2 and Rho kinase phosphorylation (2.3 ± 0.2- and 2.1 ± 0.2-fold increase over basal values, respectively), while ANG-(17) was without effect. The ANG II-mediated phosphorylation of ERK1/2 and Rho kinase was prevented in a dose-dependent manner by ANG-(17) and disappeared in the presence of the Mas receptor antagonist D-Ala7-ANG-(17). Both ANG II and ANG-(17) increased STAT3 and STAT5a/b phosphorylation to a similar extent (130140% increase). The ANG-(17)-stimulated STAT phosphorylation was blocked by the AT1 receptor antagonist losartan and not by D-Ala7-ANG-(17). Our results show a dual action of ANG-(17), that is, a stimulatory effect on STAT3 and 5a/b phosphorylation through AT1 receptors and a blocking action on ANG II-stimulated ERK1/2 and Rho kinase phosphorylation through Mas receptor activation. The latter effect could be representative of a mechanism for a protective role of ANG-(17) in the heart by counteracting the effects of locally generated ANG II.