Copyright © 1996 by the European Society of Cardiology.
© The European Society of Cardiology
Cardiovascular physiology
The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries
*Department of Clinical Pharmacology, University of Groningen Groningen, The Netherlands
Thoraxcenter, University Hospital Groningen Groningen, The Netherlands
Department of Internal Medicine, University of Regensburg Regensburg, Germany
Received 20 July 1995; accepted 7 August 1995.
Correspondence: Hendrik Buikema, PhD, Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan I, 9713 AV Groningen, The Netherlands
Abstract
We hypothesized that angiotensin-converting enzyme (ACE) insertion/deletion polymorphism may be related to arterial phenotypic differences that could explain the adverse effects of deletion polymorphism.
Accordingly, contractile responses to angiotensin I and II (0·1 nmol .1–1 µmol. 1–1), endothelium-dependent relaxation to methacholine (0·0–100 µmol . 1–1), and the effect of NG (L-NMMA; 100 .µmol . 1–1) on phenylephrine (10 µmol .1–1) induced contraction, were studied in isolated rings of internal mam mary arteries obtained from patients undergoing coronary bypass surgery. The results were analysed according to the ACE genotype of the patient (II, n=8; ID, n=11; DD, n=9) as well as the presence/absence of either allele.
The arteries from patients with the D allele (IDIDD) displayed a lower sensitivity to methacholine (P<0·05 vs II), which suggested that the capacity of the endothelium for nitric oxide release in response to stimulation was also lower. By contrast, the increase in phenylephrine-induced contraction, by pre-incubation with L-NMMA, was more pronounced in the group with the DD allele (31±5%) than with the ID (11±11%) and II alleles (1±11%, P<0·05 vs DD), 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 1, indicated that the level of angiotensin I conversion was higher in patients with the D allele (IDIDD, P<0·05 vs II).
The findings of this study indicate that ACE insertion/deletion polymorphism is related to arterial phenotypic differences in endothelial function and angiotensin I conversion.
Key Words: ACE insertion/deletion polymorphism • internal mammary artery • phenotypic differences
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