The heart is subjected to different hormonal stimulus, which influence directly or indirectly its trophic status. The angiotensin II (Ang II), characterized as the main effector of Renin-Angiotensin System (RAS), is a potent vasoactive peptide and exerts numerous biological effects through of its receptors (AT1 and AT2). In cardiac tissue, Ang II promotes cardiomyocyte hypertrophy and hyperplasia of fibroblasts. The heart corresponds to the main target of thyroid hormones (TH), which also influence the cardiac tropism. In the last years we and other authors have shown a close relationship between the cardiac hypertrophy induced by TH and the RAS activation. This way, hyperthyroid rats treated with AT1 receptor inhibitor presented prevention of hypertrophy as in vivo as in vitro. On the other hand, the AT1 inhibition did not abolish the cardioprotective effect of TH on Ischemia/Reperfusion (I/R) experimental model. Considering that: the role of AT2 receptors is not well defined in adult animals yet and recent studies have shown that I/R promotes decrease on AT2 receptor expression in the myocardium but in the hyperthyroidism the AT2 expression is increased (about 50%) in the heart, we have hypothesized that the cardioprotective effect of TH in I/R model may occur with the participation of AT2 receptor. This hypothesis will be tested using I/R experimental model in isolated hearts of AT2 knockout mice, submitted to treatment with T3 for 14 days. The role of nitric oxide synthases (NOS), also activated by high levels of TH, normally triggered in response to ischemic stress and described as responsible for the increased synthesis of nitric oxide (NO) also will be evaluated in this study.
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