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| Item Type: | Article |
|---|---|
| Title: | Ang II (angiotensin II) conversion to angiotensin-(1-7) in the circulation is POP (prolyloligopeptidase)-dependent and ACE2 (angiotensin-converting enzyme 2)-independent |
| Creators Name: | Serfozo, P., Wysocki, J., Gulua, G., Schulze, A., Ye, M., Liu, P., Jin, J., Bader, M., Myöhänen, T., García-Horsman, J.A. and Batlle, D. |
| Abstract: | The Ang II (Angiotensin II)-Angiotensin-(1-7) axis of the Renin Angiotensin System encompasses 3 enzymes that form Angiotensin-(1-7) [Ang-(1-7)] directly from Ang II: ACE2 (angiotensin-converting enzyme 2), PRCP (prolylcarboxypeptidase), and POP (prolyloligopeptidase). We investigated their relative contribution to Ang-(1-7) formation in vivo and also ex vivo in serum, lungs, and kidneys using models of genetic ablation coupled with pharmacological inhibitors. In wild-type (WT) mice, infusion of Ang II resulted in a rapid increase of plasma Ang-(1-7). In ACE2(-/-)/PRCP(-/-) mice, Ang II infusion resulted in a similar increase in Ang-(1-7) as in WT (563±48 versus 537±70 fmol/mL, respectively), showing that the bulk of Ang-(1-7) formation in circulation is essentially independent of ACE2 and PRCP. By contrast, a POP inhibitor, Z-Pro-Prolinal reduced the rise in plasma Ang-(1-7) after infusing Ang II to control WT mice. In POP(-/-) mice, the increase in Ang-(1-7) was also blunted as compared with WT mice (309±46 and 472±28 fmol/mL, respectively =0.01), and moreover, the rate of recovery from acute Ang II-induced hypertension was delayed (=0.016). In ex vivo studies, POP inhibition with ZZP reduced Ang-(1-7) formation from Ang II markedly in serum and in lung lysates. By contrast, in kidney lysates, the absence of ACE2, but not POP, obliterated Ang-(1-7) formation from added Ang II. We conclude that POP is the main enzyme responsible for Ang II conversion to Ang-(1-7) in the circulation and in the lungs, whereas Ang-(1-7) formation in the kidney is mainly ACE2-dependent. |
| Keywords: | Angiotensins, Hypertension, Renin-Angiotensin System, Animals, Mice |
| Source: | Hypertension |
| ISSN: | 0194-911X |
| Publisher: | American Heart Association |
| Volume: | 75 |
| Number: | 1 |
| Page Range: | 173-182 |
| Date: | January 2020 |
| Additional Information: | Copyright © 2019 American Heart Association, Inc. |
| Official Publication: | https://doi.org/10.1161/HYPERTENSIONAHA.119.14071 |
| External Fulltext: | View full text on PubMed Central |
| PubMed: | View item in PubMed |
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