title: Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene.
abstract: We utilized mice with homozygous disruption of angiotensin-converting enzyme (ACE) (-/-), mice with heterozygous deletion of ACE (+/-), and wild-type mice (+/+) to test the hypothesis that genetic variation in ACE modulates tissue and plasma angiotensin (ANG) II concentrations. With the use of ANG I as substrate, kidney, heart, and lung ACE activity was reduced 80% in -/- mice compared with +/+ mice. However, ANG II concentrations and ANG II-to-ANG I ratios in the kidney, heart, and lung did not differ among genotypes. In contrast, plasma ANG II concentrations in -/- mice were <2 fmol/ml, whereas plasma ANG I concentrations were extremely high (765 fmol/ml). Chymase activity was increased 14-fold in the kidney (P < 0.05) and 1.5-fold in the heart (P < 0.05) of -/- versus +/+ mice but did not differ among genotypes in the lung. ANG II formation from enzymes other than ACE and chymase contributed <2% of total ANG II formation in all genotypes. These data suggest that ACE is essential to ANG II formation in the vascular space, whereas chymase may provide an important mechanism in maintaining steady-state ANG II levels in tissue.
authors: Birmingham Veteran Affairs Medical Center and Division of Cardiovascular Disease, Department of Medicine, Vascular Biology and Hypertension Program, University of Alabama, Birmingham, Alabama 35294, USA.
authors: Chih-Chang
authors: CC
authors: Wei
authors: Baohong
authors: B
authors: Tian
authors: Gilbert
authors: G
authors: Perry
authors: Qing Cheng
authors: QC
authors: Meng
authors: Yiu-Fai
authors: YF
authors: Chen
authors: Suzanne
authors: S
authors: Oparil
authors: Louis J
authors: LJ
authors: Dell'Italia
mesh_terms: D000803:Angiotensin I / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D053818:Chymases; D015870:Gene Expression; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases