Pathways of angiotensin-(1-7) metabolism in the kidney

Angiotensin-(1-7) [Ang-(1-7)], which can be formed directly from angiotensin I (Ang I) bypassing the requisite production of Ang II, is a bioactive component of the renin-angiotensin system that may oppose the actions of Ang II. In contrast to the generation of Ang II, angiotensin-converting enzyme (ACE) hydrolyses Ang-(1-7) to inactive fragments. ACE inhibitors substantially augment circulating levels of Ang-(1-7) and increase the peptide's half-life. Thus, this enzymatic pathway constitutes a key regulatory point in the vasculature to balance the actions of Ang II, Ang-(1-7) and bradykinin. In contrast, the renal pathways for the metabolism of Ang-(1-7) appear quite distinct. Characterization of this pathway may shed new light on the potential actions of the peptide in the kidney, as well as the mechanisms of novel vasoactive peptidase therapies. We summarize recent experimental and clinical studies that begin to reveal novel pathways in the formation and degradation of Ang-(1-7) in the kidney.