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| Item Type: | Article |
|---|---|
| Title: | Angiotensin-(1-12): does it exist? A critical evaluation in humans, rats, and mice |
| Creators Name: | Rodrigues, A.F., Domenig, O., Poglitsch, M., Bader, M. and Danser, A.H.J. |
| Abstract: | BACKGROUND: Angiotensin-(1-12), measured by a self-developed, polyclonal antibody-based radioimmunoassay, has been suggested to act as an alternative precursor of angiotensin II. A more reliable detection method would be liquid chromatography-tandem mass spectrometry. METHODS: We set up the quantification of human and murine angiotensin-(1-12) by liquid chromatography-tandem mass spectrometry and then used this method to measure angiotensin-(1-12) in human and mouse blood samples, as well as in mouse brain and kidney. We also verified ex vivo angiotensin-(1-12) generation and metabolism in human blood samples incubated at 37 °C. RESULTS: Stabilization of blood in guanidine hydrochloride was chosen for sample collection since this allowed full recovery of spiked angiotensin-(1-12). Angiotensin-(1-12) was undetectable in human blood samples when incubating nonstabilized plasma at 37 °C, while angiotensin-(1-12) added to nonstabilized human plasma disappeared within 10 minutes. Stabilized human blood samples contained angiotensin II, while angiotensin-(1-12) was undetectable. Blood, hearts, and kidneys, but not brains, of wild-type mice and rats contained detectable levels of angiotensin II, while angiotensin-(1-12) was undetectable. In renin knockout mice, all angiotensins, including angiotensin-(1-12), were undetectable at all sites, despite a 50% rise in angiotensinogen. Angiotensin-(1-12) metabolism in human blood plasma was not affected by renin inhibition. Yet, blockade of angiotensin-converting enzyme and aminopeptidase A, but not of chymase, neutral endopeptidase, or prolyl oligopeptidase, prolonged the half-life of angiotensin-(1-12), and angiotensin-converting enzyme inhibition prevented the formation of angiotensin II. CONCLUSIONS: We were unable to detect intact angiotensin-(1-12) in humans or mice, either in blood or tissue, suggesting that this metabolite is an unlikely source of endogenous angiotensins. |
| Keywords: | Angiotensin II, Angiotensinogen, Chromatography, Liquid, Mice, Knockout, Tandem Mass Spectrometry, Animals, Mice, Rats |
| Source: | Hypertension |
| ISSN: | 0194-911X |
| Publisher: | American Heart Association |
| Volume: | 81 |
| Number: | 8 |
| Page Range: | 1776-1784 |
| Date: | August 2024 |
| Official Publication: | https://doi.org/10.1161/HYPERTENSIONAHA.124.22856 |
| PubMed: | View item in PubMed |
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