New Cardiovascular and Pulmonary Therapeutic Strategies Based on the Angiotensin-Converting Enzyme 2/Angiotensin-(1–7)/Mas Receptor Axis

Ferreira, Anderson J.; Murça, Tatiane M.; Fraga-Silva, Rodrigo A.; Castro, Carlos Henrique; Raizada, Mohan K.; Santos, Robson A. S.

As the major enzyme involved in Ang-(1-7) formation, ACE2 has also a crucial role in vessels. Lovren et al. [111] have demonstrated that ACE2 ameliorates the endothelial homeostasis via a mechanism involving reduction of the reactive oxygen species production [111] . Of note, this effect was attenuated by A-779 [111] . Moreover, overexpression of ACE2 in vessels of hypertensive rats resulted in reduction in the arterial blood pressure and improvement of the endothelial function associated with increased circulating Ang-(1-7) levels [112] . Overall, these data indicate that the beneficial effects of ACE2 are, at least in part, mediated by Ang- (1-7) . Recently, we have demonstrated that activation of endogenous ACE2 causes a dose-dependent hypotensive effect in normotensive and hypertensive rats [113] . Also, the response to Bk administration was augmented in rats chronically treated with XNT, an ACE2 activator [113] . However, we were unable to demonstrate any significant effect of XNT on blood pressure in response to the administration of Ang II or Losartan in normotensive and hypertensive rats ( Figure 2 ).