THE DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING ENZYME GENE IS RELATED TO PHENOTYPIC DIFFERENCES IN HUMAN ARTERIES

We hypothesized that angiotensin-converting enzyme (ACE) insertion/del etion polymorphism may be related to arterial phenotypic differences t hat could explain the adverse effects of deletion polymorphism. Accord ingly, contractile responses to angiotensin I and II (0.1 nmol.l(-1)-1 mu mol.l(-1)), endothelium-dependent relaxation to methacholine (0.01 -100 mu mol.l(-1)), and the effect of N-G-monomethyl-L-arginine (L-NMM A; 100 mu mol.l(-1)) on phenylephrine (10 mu mol.l(-1)) induced contra ction, were studied in isolated rings of internal mammary arteries obt ained from patients undergoing coronary bypass surgery. The results we re analysed according to the ACE genotype of the patient (II: n = 8; I D, n = 11, DD, n = 9) as well as the presence/absence of either allele . The arteries from patients with the D allele (ID/DD) displayed a low er sensitivity to methacholine (P < 0.05 vs II), which suggested that the capacity of the endothelium for nitric oxide release in response t o stimulation was also lower. By contrast, the increase in phenylephri ne-induced contraction, by pre-incubation with L-NMMA, was more pronou nced in the group with the DD allele (31 +/- 5%) than with the ID (11 +/- 11%) and II alleles (1 +/- 11%, P < 0.05 vs no), which suggested a higher level of basal nitric oxide release. Finally, the differences in the responses to angiotensin I and II, which were used to evaluate the vascular conversion of angiotensin I, indicated that the level of angiotensin I conversion was higher in patients with the D allele (ID/ DD, P < 0.05 vs II). The findings of this study indicate that ACE inse rtion/deletion polymorphism is related to arterial phenotypic differen ces in endothelial function and angiotensin I conversion.