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Vascular effects of quinapril completely depend on ACE insertion/deletion polymorphism

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands, a.a.voors{at}thorax.azg.nl

Peter P van Geel

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

Margreeth Oosterga

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

Hendrik Buikema

Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

Dirk J van Veldhuisen

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

Wiek H van Gilst

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands, Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

Introduction

The angiotensin-converting enzyme (ACE) DD-genotype is associated with increased plasma and myocardial ACE-activity. The influence of the ACE insertion/deletion (I/D) polymorphism on the effects of ACE-inhibition on vascular responses has not been previously described.

Materials and methods

In the randomised, double-blind QUinapril On Vascular ACE and Determinants of Ischemia Study (QUO VADIS), 149 patients undergoing coronary bypass surgery were randomised to receive either the ACE inhibitor, quinapril, or placebo. In 82 patients, we obtained ACE-genotype, and measured vascular responses to angiotensin II (Ang II) in left internal mammary arteries.

Results

In the placebo group, the mean maximal vasoconstriction to Ang II was significantly lower in patients with the DD-genotype than in those with the ID/II genotype (36.2±5.11% [n=13] vs. 55.6±4.57% [n=25]; p=0.01). In the quinapril group, the mean maximal vasoconstriction to Ang II was similar [n=8] vs. 57.7±4.07% [n=35]; p=0.85). between DD- and ID/II-genotype (59.6±9.19%

Conclusions

DD-genotype patients showed decreased vascular responses to Ang II but treatment with quinapril completely restored the decreased vascular response in DD-genotype patients to the same level as II/ID-genotype patients, while no effect of quinapril was demonstrated in the II/ID-genotype patients.

Key Words: angiotensin • arteries • bypass • vasoconstriction • vessels

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 3, 130-134 (2004)
DOI: 10.3317/jraas.2004.029


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