However, normal ACE2 enzymatic activity in plasma is very low, probably due to the presence of an endogenous inhibitor [17] [18] [19] . ACE2 is different from ACE in both substrate specificity and functions [9, 20, 21] . ACE2 can form (a) Ang-(1-7) through hydrolysis of Ang II and (b) Ang-(1-9) through hydrolysis of Ang I. This last reaction is negligibly slow and is several hundred times slower than Ang II hydrolysis by ACE2 to form Ang(1-7)-a vasodepressor peptide counterbalancing the vasopressor effect of Ang II [20, 21] . Ang-(1-7) can be subsequently converted to Ang-(1-5) by ACE [9, 20] or by neutral endopeptidases [9] , while Ang-(1-9) may be converted to Ang-(1-7) by ACE [9] . There is little evidence proving the existence of alternative hydrolysis of Ang-(1-9) to Ang II in some tissues. Drummer et al. [22] proved that homogenates of rat kidney, and in a lesser extent of lung, convert Ang-(1-9) to Ang II due to an ACEindependent aminopeptidase and N-like carboxypeptidase. Singh et al. [23] confirmed that the pathway Ang I-Ang-(1-9)-Ang II really exists in glomeruli of streptozotocininduced diabetes mellitus rats. Moreover, in human heart tissue the main products of Ang I degradation are both Ang-(1-9) and Ang II generated by heart chymase, ACE and a poorly identified carboxypeptidase A [24] . Although the data proving the existence of alternative pathways of Ang II production, in clinical practice we can still block only ACE or AT1R.