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.

The relevance of the RAS is highlighted by the success obtained in therapeutic strategies based on the pharmacological inhibition of this system in cardiovascular and respiratory diseases [27] [28] [29] [30] [31] [32] . Blockade of the RAS with ACE inhibitors (ACEi) or AT 1 receptor antagonists (ARBs) improves the outcomes of patients with hypertension, acute myocardial infarction, and chronic systolic heart failure [33] [34] [35] . Furthermore, based on the involvement of the ACE/Ang II/AT 1 axis in respiratory diseases and the crucial role of the lungs in the RAS metabolism, several studies have reported the contribution of the RAS in lung pathophysiology [28, 30, 31, [36] [37] [38] [39] [40] . Importantly, it has been shown that administration of ACEi and ARBs causes substantial increases in plasma Ang-(1-7) levels, leading to the assumption that part of their clinical effects might be mediated by this heptapeptide [41] [42] [43] . Indeed, some effects of ACEi and ARBs can be blocked or attenuated by A-779, a Mas antagonist, confirming the role of Ang- (1) (2) (3) (4) (5) (6) (7) in the actions of these compounds [44] . The beneficial effects of Ang-(1-7), as well as its likely participation in the effects of the ACEi and ARBs, represent evidences for the potential of the ACE2/Ang-(1-7)/Mas axis as a therapeutic target.