Some studies have suggested that Ang-(1-9) may be an endogenous inhibitor of ACE. Donoghue et al. [9] proposed that Ang-(1-9) is a competitive inhibitor of ACE because it is by itselfan ACE substrate. Under conditions of ACE inhibition, such as after long-term administration of an ACEI in rats, Ang-(1-9) levels increased in plasma and kidney [50, 53] . This increase in Ang-(1-9) steady-state levels could be due to decreased catabolism of Ang-(1-9) by ACE. Conversely, the increased levels of Ang-(1-9) could be due to increased production by ACE2 as a result of increased availability of Ang I substrate. These results indicate that an alternate pathway of Ang I metabolism by ACE2 exists and that this pathway may be amplified in the presence of ACE inhibitors.