This work was supported by the Coordenadoria de Aperfeiçoamento do Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). “
“It has become apparent that the biologically active member

of the renin-angiotensin system (RAS), the heptapeptide Angiotensin (Ang)-(1-7), holds cardioprotective actions [4], [5], [18] and [23]. This peptide is formed through the degradation of Ang II by the angiotensin-converting enzyme (ACE) homolog, ACE2, yet other enzymes such as the metallopeptidase neprilysin are also able to produce Ang-(1-7) directly from Ang I [23]. However, recent reports have indicated that ACE2 is the principal enzyme check details and pathway involved in the Ang-(1-7) generation

in key organs as heart and kidney [11] and [26]. Under physiological and pathological states, it is now recognized that Ang-(1-7) opposes many cardiac actions of Ang Bafilomycin A1 nmr II by binding to the Mas receptor [22], and triggering signaling pathways leading to vasodilation, anti-fibrotic, anti-hypertrophic and anti-arrhythmic actions [5], [8] and [23]. Functionally, the confirmation that Mas is a receptor for Ang-(1-7) came from mice which present genetic deletion of this receptor (Mas knockout mice). For example, the vasodilator effect of Ang-(1-7) is absent in these mice [13]. Moreover, Mas knockout mice showed pronounced impairment of the cardiac [3] and [24] and renal functions [16] and Mas deficiency leads to dramatic changes in glucose and lipid metabolisms, inducing a Cell press metabolic syndrome-like state [25]. It is known that the expression and/or activity of

the major enzymes, peptides and receptors of the RAS change according to different pathophysiological conditions of the heart. Furthermore, these changes depend on the stage of the disease. For example, Ishiyama et al. [10] found a reduction in AT1 expression in the chronic phase of the myocardial infarction (MI)-induced cardiac remodeling (28 days). Importantly, these alterations occurred without modifications of cardiac ACE and ACE2 mRNA levels. In addition, Ocaranza et al. [15] observed an increase in cardiac ACE2 activity after 1 week of MI followed by a reduction in its activity after 8 weeks of the injury. Reduced cardiac expression of AT2 was also observed in the early post injury period in infarcted hearts, but not at the later failure stage [12]. Previous studies have also investigated the levels of Ang II and Ang-(1-7) in the injured heart. While Zhang et al. [27] reported an increase in Ang I and Ang II immunoreactivity in the heart of adult rats after 7 days of coronary artery narrowing, Santiago et al. [21] found no significant differences in Ang-(1-7) levels in the left ventricles of DOCA-salt hypertensive rats when compared to their controls.