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

Angiotensin-(1-7) [Ang-(1-7)], which can be formed directly from angiotensi n I (Ang I) bypassing the requisite :production of Ang II, is a bioactive c omponent 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 substanti ally augment circulating levels of Ang-(1-7) and-increase the peptide's hal f-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 qui te distinct. Characterization of this pathway may shed new light on the pot ential actions of the peptide in the kidney, as well as the mechanisms of n ovel vasoactive peptidase therapies. We summarize recent experimental and c linical studies that begin to reveal novel pathways in the formation and de gradation of Ang-(1-7) in the kidney.