ACE2 and ACE are two zinc metalloprotease that function differently despite their similarities. ACE2 is a monocarboxypeptidase (cleaves a C-terminal single amino acid from its substrate), whereas ACE is a dipeptidylpeptidase (releases a C-terminal dipeptide from its substrate) [86,87]. ACE2 has a substrate preference for hydrolysis between proline and a hydrophobic or basic C-terminal residue [79,86,87] and acts not only on the RAS and bradykinin peptides but also on the C-terminus of the apelin, casomorphin dynorphin peptides [79], possibly inhibiting Apelin-13 hypotensive action [44]. It is expressed in the heart, kidneys, liver, colon, small intestine, lung, brain and testes [39,44,45,46,76,77,87]. Among the tissues expressing ACE2 there are cardiomyocytes, endothelium, alveolar type II cells, ciliated airway cells, vascular smooth muscle cells and testicular Leydig cells [14,39,44,45,46,76,77,87,88,89]. ACE2 is present on the apical surface of epithelial cells of renal tubules, lung alveoli and vascular endothelia, in these last cells the production of Ang (1–7) induces autocrine activation of MasR axis leading to NOS-mediated vasodilation and consequently hypotension [14,44,45,46,86,87,88,89].