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


METHODS
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.


CONCLUSIONS
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.
Alexiou
Theodora
T
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
Boon
Wee Ming
WM
Denton
Derek A
DA
Nicolantonio
Robert Di
RD
Walker
Lesley L
LL
McKinley
Michael J
MJ
Campbell
Duncan J
DJ
D000808:Angiotensinogen / Q000235:genetics*; D000809:Angiotensins / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D001920:Bradykinin / Q000032:analysis* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*
D000809:Angiotensins; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin