Functional consequences of angiotensin-converting enzyme gene polymorphism on N-acetyl-Ser-Asp-Lys-Pro degradation and angiotensin II production.
Studies analyzing the biochemical and hemodynamic consequences of the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme gene on angiotensin I and bradykinin metabolism have provided divergent results. Twelve DD and 12 II normotensive subjects were infused for 15 min with angiotensin I (30 ng kg(-1) x min(-1)) and with another angiotensin I converting enzyme substrate not related to the renin-angiotensin system, N-acetyl-Ser-Asp-Lys-Pro (AcSDKP; 1.12 micro g kg(-1) x min(-1)), in the presence and absence of captopril. The infusion of the two peptides was repeated 15 days apart. In both the presence and the absence of captopril we found that DD and II subjects did not significantly differ in terms of endogenous plasma AcSDKP, angiotensin I, or angiotensin II concentrations, and that conversion of exogenous angiotensin I to angiotensin II was not faster in the DD subjects. Exogenously infused AcSDKP was metabolized slightly more rapidly in DD than in II subjects only when angiotensin I converting enzyme was not inhibited. The within-subject variability for angiotensin measurements was high, in contrast to AcSDKP measurements. This variability may account for the divergent results reported to date in the biochemical consequences of the I/D polymorphism of the angiotensin I converting enzyme gene. In conclusion, the I/D polymorphism of the angiotensin I converting enzyme gene has no effect on either endogenous AcSDKP metabolism or on the circulating renin-angiotensin system. It slightly affects the metabolism of exogenously infused AcSDKP and not that of angiotensin I.
Azizi
Michel
M
Centre d'Investigations Cliniques 9201, Assistance Publique des Hôpitaux de Paris et INSERM, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris cedex 15, France. michel.azizi@egp.ap-hop-paris.fr
Junot
Christophe
C
Ezan
Eric
E
Hallouin
Marie-Charlotte
MC
Guyene
Tam
T
Ménard
Joël
J
D000293:Adolescent; D000328:Adult; D000803:Angiotensin I / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011110:Polymorphism, Genetic; D016037:Single-Blind Method; D013379:Substrate Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C058504:goralatide