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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Blockage of Angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation

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Author(s):
Carneiro-Ramos, M. S. [1, 2] ; Diniz, G. P. [3] ; Nadu, A. P. [4] ; Almeida, J. [4] ; Vieira, R. L. P. [4] ; Santos, R. A. S. [4] ; Barreto-Chaves, M. L. M. [3]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508900 Sao Paulo - Brazil
[2] Fed Univ ABC, Nat & Human Sci Ctr, Santo Andre - Brazil
[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Anat, Lab Biol Celular & Anat Func, BR-05508900 Sao Paulo - Brazil
[4] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil
Total Affiliations: 4
Document type: Journal article
Source: BASIC RESEARCH IN CARDIOLOGY; v. 105, n. 3, p. 325-335, MAY 2010.
Web of Science Citations: 29
Abstract

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. (AU)