Novel roles of the renal angiotensin-converting enzyme.
Mol Cell Endocrinol
; 529: 111257, 2021 06 01.
Article
in En
| MEDLINE
| ID: mdl-33781839
ABSTRACT
The observation that all components of the renin angiotensin system (RAS) are expressed in the kidney and the fact that intratubular angiotensin (Ang) II levels greatly exceed the plasma concentration suggest that the synthesis of renal Ang II occurs independently of the circulating RAS. One of the main components of this so-called intrarenal RAS is angiotensin-converting enzyme (ACE). Although the role of ACE in renal disease is demonstrated by the therapeutic effectiveness of ACE inhibitors in treating several conditions, the exact contribution of intrarenal versus systemic ACE in renal disease remains unknown. Using genetically modified mouse models, our group demonstrated that renal ACE plays a key role in the development of several forms of hypertension. Specifically, although ACE is expressed in different cell types within the kidney, its expression in renal proximal tubular cells is essential for the development of high blood pressure. Besides hypertension, ACE is involved in several other renal diseases such as diabetic kidney disease, or acute kidney injury even when blood pressure is normal. In addition, studies suggest that ACE might mediate at least part of its effect through mechanisms that are independent of the Ang I conversion into Ang II and involve other substrates such as N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), Ang-(1-7), and bradykinin, among others. In this review, we summarize the recent advances in understanding the contribution of intrarenal ACE to different pathological conditions and provide insight into the many roles of ACE besides the well-known synthesis of Ang II.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Renin-Angiotensin System
/
Angiotensin I
/
Peptidyl-Dipeptidase A
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Diabetic Nephropathies
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Acute Kidney Injury
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Hypertension
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell Endocrinol
Year:
2021
Document type:
Article