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


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 between DD- and ID/II-genotype (59.6+/-9.19% [n=8] vs. 57.7+/-4.07% [n=35]; p=0.85).


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.
Voors
Adriaan A
AA
Department of Cardiology, Thoraxcenter, University Hospital of Groningen, Groningen 9700, The Netherlands. a.a.voors@thorax.azg.nl
van Geel
Peter P
PP
Oosterga
Margreeth
M
Buikema
Hendrik
H
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D004251:DNA Transposable Elements; D004311:Double-Blind Method; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects* / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D000077583:Quinapril; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004251:DNA Transposable Elements; D044005:Tetrahydroisoquinolines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril