Document Detail

Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation.
MedLine Citation:
PMID:  20155476     Owner:  NLM     Status:  MEDLINE    
Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2 receptor (AT(2)R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT(2)R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT(2)R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT(2) blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.
M S Carneiro-Ramos; G P Diniz; A P Nadu; J Almeida; R L P Vieira; R A S Santos; M L M Barreto-Chaves
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-14
Journal Detail:
Title:  Basic research in cardiology     Volume:  105     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-03-03     Completed Date:  2010-05-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  325-35     Citation Subset:  IM    
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S?o Paulo, S?o Paulo, Brazil.
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MeSH Terms
Angiotensin II / physiology
Cells, Cultured
Disease Models, Animal
Heart Diseases / chemically induced*,  physiopathology,  prevention & control*
Hyperthyroidism / physiopathology
Hypertrophy / chemically induced,  physiopathology,  prevention & control
Imidazoles / pharmacology
Myocardium / pathology*
Myocytes, Cardiac / drug effects,  pathology
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*,  physiology
Pyridines / pharmacology
Rats, Wistar
Receptor, Angiotensin, Type 1 / physiology
Receptor, Angiotensin, Type 2 / antagonists & inhibitors*,  physiology
Signal Transduction / physiology
Thyroxine / adverse effects*
Reg. No./Substance:
0/Imidazoles; 0/Pyridines; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 11128-99-7/Angiotensin II; 130663-39-7/PD 123319; 7488-70-2/Thyroxine; EC Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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