title: ACE insertion/deletion genotype affects bradykinin metabolism.
abstract: A deletion allele of the angiotensin-converting enzyme (ACE) gene has been associated with increased serum ACE activity, enhanced conversion of angiotensin (Ang) I to Ang II, and cardiovascular morbidity. This study tested the hypothesis that the ACE deletion allele is also associated with enhanced degradation of bradykinin, a vasoprotective peptide. Metabolism of synthetic bradykinin was measured in sera obtained from subjects who were homozygous for either the ACE deletion (n=12) or insertion (n=8) allele and who had participated in an Ang I-infusion protocol. ACE levels tended to be increased in subjects who were DD compared with those who were II [41.2 (95% CI, 27.9, 54.3) vs. 28.0 IU/L (20.0, 35.9); t=-1.6; p=0.1 18]. During Ang I infusion, plasma Ang II concentrations were increased in DD compared with II subjects (F =4.4; p=0.052). In contrast, the half-life of bradykinin was significantly decreased in sera obtained from ACE DD compared with II subjects [26.3 s (17.8, 34.6 s) vs. 42.1 s (24.4, 59.9 s); t=-2.4; p=0.029]. Moreover, there were significant inverse relations between the half-life of bradykinin and serum ACE activity (p < 0.001) and between the half-life of bradykinin and the conversion of Ang I to Ang II (p=0.026). This study confirms that ACE genotype determines bradykinin degradation and suggests another mechanism whereby the ACE D allele could be associated with deleterious cardiovascular effects.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6602, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Blais
authors.forename: S K
authors.initials: SK
authors.lastname: Gandhi
authors.forename: A
authors.initials: A
authors.lastname: Adam
mesh_terms: D000328:Adult; D001920:Bradykinin / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*
chemical_list: D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin