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Plasma and Kidney Angiotensin Peptides: Importance of the Aminopeptidase A/Angiotensin III Axis
- Source :
- American Journal of Hypertension. 28:1418-1426
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
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.
- Subjects :
- Male
medicine.medical_specialty
Angiotensins
Angiotensin III
Peptide
Peptidyl-Dipeptidase A
Glutamyl Aminopeptidase
Kidney
Aminopeptidase
Renin-Angiotensin System
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Animals
Mice, Knockout
chemistry.chemical_classification
business.industry
Angiotensin II
Mice, Inbred C57BL
Enzyme
Endocrinology
medicine.anatomical_structure
chemistry
Angiotensin-converting enzyme 2
cardiovascular system
Female
Original Article
Angiotensin-Converting Enzyme 2
business
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 19417225 and 08957061
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- American Journal of Hypertension
- Accession number :
- edsair.doi.dedup.....196dcae17c9dcd8e62c4c8da8bfea85c