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Am J Hypertens. 2015 Dec;28(12):1418-26. doi: 10.1093/ajh/hpv054. Epub 2015 May 11.

Plasma and Kidney Angiotensin Peptides: Importance of the Aminopeptidase A/Angiotensin III Axis.

Author information

1
Division of Nephrology & Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
2
Division of Nephrology & Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. d-batlle@northwestern.edu.

Abstract

BACKGROUND:

The renin-angiotensin system is a complex regulatory hormonal network with a main biological peptide and therapeutic target, angiotensin (Ang) II (1-8). There are other potentially important Ang peptides that have not been well evaluated.

METHODS:

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for concurrent evaluation of multiple Angs downstream of Ang I (1-10) and Ang II (1-8) in kidney and plasma from wild-type (WT) mice. Angiotensin converting enzyme 2 knockout (ACE2KO) was also used as a way to examine the Angs profile in the absence of ACE2, an enzyme that cleaves both Ang I (1-10) and Ang II (1-8).

RESULTS:

In plasma from both WT and ACE2KO, levels of Ang I (1-10), Ang III (2-8), and Ang (2-10) were the highest of all the renin-angiotensin system (RAS) peptides. The latter two peptides are products of aminopeptidase A cleavage of Ang II (1-8) and Ang I (1-10), respectively. In contrast, plasma levels of Ang II (1-8), and Ang (1-7), the product of Ang II (1-8) cleavage by ACE2, were low. In kidney from both WT and ACE2KO, Ang II (1-8) levels were high as compared to plasma levels. In the ACE2KO mice, a significant increase in either Ang II (1-8) or a decrease in Ang (1-7) was not observed in plasma or in the kidney.

CONCLUSION:

RAS-focused peptidomic approach revealed major differences in Ang peptides between mouse plasma and kidney. These Ang peptide profiles show the dominance of the aminopeptidase A/Ang (2-10) and aminopeptidase A/Ang III (2-8) pathways in the metabolism of Ang I (1-10) and Ang II (1-8) over the ACE2/Ang (1-7) axis. Ang III (2-8) and other peptides formed from aminopeptidase A cleavage may be important therapeutic RAS targets.

KEYWORDS:

ACE2; aminopeptidase A; angiotensin (1–7); blood pressure; hypertension.; angiotensin II; angiotensin III

PMID:
25968123
PMCID:
PMC4757941
DOI:
10.1093/ajh/hpv054
[Indexed for MEDLINE]
Free PMC Article

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