ACE I/D Genotype Determines in Vivo Bradykinin Metabolism in Humans
Bradykinin (BK)is a cardioprotective peptide that is inactivated by ACE. An insertion(I)/deletion(D) polymorphism in the ACE gene determines plasma ACE levels. The D allele is associated with increased cardiovascular morbidity and mortality. These correlations may be due to increased conversion of Ang I to Ang II or, alternativley, to increased degradation of BK to its inactive product BK1-5. We determined the effect of ACE I/D on in vivo BK metabolism. BK (400 ng/min) was infused into the brachial artery of volunteers homozygous for the ACE I or D allele. Forearm venous blood was analyzed for BK and BK1-5 using a sensitive and specific liquid chromatography-mass spectroscopy method. ACE activity, venous BK1-5 conentration and BK1-5:BK ratio were higher in D/D vs I/I subjects, while BK tended to be lower (Table). Total kinin concentration in venous blood correlated with net t-PA release across the forearm (r2=0.51, P=0.0012). The ACE I/D polymorphism determines the in vivo degradation of BK in humans. The ratio of BK1-5:BK may serve as a marker for tissue ACE activity.