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Angiotensinogen and angiotensin-converting enzyme gene copy number and angiotensin and bradykinin peptide levels in mice

journal contribution
posted on 2005-05-01, 00:00 authored by T Alexiou, W M Boon, D A Denton, Robert Di Nicolantonio, L L Walker, M J McKinley, D J Campbell
OBJECTIVE: To test the hypothesis that changes in gene expression that may accompany angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphism cause alteration in angiotensin and bradykinin peptide levels. DESIGN: Mice with one or two genes for AGT and ACE allow assessment of the effects of modest alteration in AGT and ACE gene expression on angiotensin and bradykinin peptide levels. METHODS: Angiotensin and bradykinin peptides were measured in the blood, kidney, heart, lung, adrenal, brain, and aorta of mice that were either wild-type (+/+), heterozygous (+/-) or null (-/-) for either the AGT or ACE gene. RESULTS: Angiotensin I and angiotensin II were not detectable in blood or tissues of AGT -/- mice, which had increased bradykinin levels in kidney and lung. ACE -/- mice had markedly reduced angiotensin II levels and increased bradykinin levels in blood and tissues. However, despite reduced AGT and ACE gene expression, angiotensin and bradykinin peptide levels in AGT and ACE +/- mice were no different from the levels in wild-type mice. CONCLUSION: Although the AGT and ACE genes are fundamental determinants of angiotensin and bradykinin peptide levels, compensatory mechanisms attenuate the effect of modest change in AGT and ACE gene expression on the levels of these peptides. Identification of these compensatory mechanisms may provide new candidate genes for investigation in humans.

History

Journal

Journal of hypertension

Volume

23

Issue

5

Pagination

945 - 954

Publisher

Lippincott Williams & Wilkins

Location

London, Eng.

ISSN

0263-6352

eISSN

1473-5598

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, Lippincott Williams & Wilkins