Voors Adriaan A, van Geel Peter P, Oosterga Margreeth, Buikema Hendrik, van Veldhuisen Dirk J, van Gilst Wiek H
Department of Cardiology, Thoraxcenter, University Hospital of Groningen, Groningen 9700, The Netherlands.
J Renin Angiotensin Aldosterone Syst. 2004 Sep;5(3):130-4. doi: 10.3317/jraas.2004.029.
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.
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.
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).
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.
血管紧张素转换酶（ACE）DD基因型与血浆及心肌ACE活性增加相关。此前尚未描述ACE插入/缺失（I/D）多态性对ACE抑制作用于血管反应的影响。
在随机、双盲的喹那普利对血管ACE及缺血决定因素研究（QUO VADIS）中，149例行冠状动脉搭桥手术的患者被随机分配接受ACE抑制剂喹那普利或安慰剂。在82例患者中，我们获取了ACE基因型，并测量了左乳内动脉对血管紧张素II（Ang II）的血管反应。
在安慰剂组中，DD基因型患者对Ang II的平均最大血管收缩反应显著低于ID/II基因型患者（36.2±5.11% [n = 13] 对55.6±4.57% [n = 25]；p = 0.01）。在喹那普利组中，DD基因型和ID/II基因型患者对Ang II的平均最大血管收缩反应相似（59.6±9.19% [n = 8] 对57.7±4.07% [n = 35]；p = 0.85）。
DD基因型患者对Ang II的血管反应降低，但喹那普利治疗可使DD基因型患者降低的血管反应完全恢复至与II/ID基因型患者相同的水平，而喹那普利对II/ID基因型患者未显示出作用。
