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Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3',5'-cyclic monophosphate-dependent pathway

Item Type:Article
Title:Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3',5'-cyclic monophosphate-dependent pathway
Creators Name:Gomes, E.R. and Lara, A.A. and Almeida, P.W. and Guimaraes, D. and Resende, R.R. and Campagnole-Santos, M.J. and Bader, M. and Santos, R.A. and Guatimosim, S.
Abstract:The renin-angiotensin (Ang) system plays a pivotal role in the pathogenesis of cardiovascular disease, with Ang II being the major effector of this system. Multiple lines of evidence have shown that Ang-(1-7) exerts cardioprotective effects in the heart by counterregulating Ang II actions. The questions that remain are how and where Ang-(1-7) exerts its effects. By using a combination of molecular biology, confocal microscopy, and a transgenic rat model with increased levels of circulating Ang-(1-7) (TGR[A1-7]3292), we evaluated the signaling pathways involved in Ang-(1-7) cardioprotection against Ang II-induced pathological remodeling in ventricular cardiomyocytes. Rats were infused with Ang II for 2 weeks. We found that ventricular myocytes from TGR(A1-7)3292 rats are protected from Ang II pathological remodeling characterized by Ca(2+) signaling dysfunction, hypertrophic fetal gene expression, glycogen synthase kinase 3beta inactivation, and nuclear factor of activated T-cells nuclear accumulation. Moreover, cardiomyocytes from TGR(A1-7)3292 rats infused with Ang II presented increased expression levels of neuronal NO synthase. To provide a signaling pathway involved in the beneficial effects of Ang-(1-7), we treated neonatal cardiomyocytes with Ang-(1-7) and Ang II for 36 hours. Treatment of cardiomyocytes with Ang-(1-7) prevented Ang II-induced hypertrophy by modulating calcineurin/nuclear factor of activated T-cell signaling cascade. Importantly, antihypertrophic effects of Ang-(1-7) on Ang II-treated cardiomyocytes were prevented by N(G)-nitro-L-arginine methyl ester and 1H-1,2,4oxadiazolo4,2-aquinoxalin-1-one, suggesting that these effects are mediated by NO/cGMP. Taken together, these data reveal a key role for NO/cGMP as a mediator of Ang-(1-7) beneficial effects in cardiac cells.
Keywords:Cardiomyocytes, NO, cGMP, Ca(2+) Transient, Ang-(1-7), Ang II, Animals, Rats
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:55
Number:1
Page Range:153-160
Date:January 2010
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.109.143255
PubMed:View item in PubMed

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