Ueda S, Meredith P A, Morton J J, Connell J M, Elliott H L
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Circulation. 1998 Nov 17;98(20):2148-53. doi: 10.1161/01.cir.98.20.2148.
We have investigated the possible effects of contrasting ACE (I/D) genotypes on the responses to the ACE inhibitor enalaprilat in normotensive men.
Subjects with DD (n=12) and II (n=11) ACE genotypes received an intravenous infusion of enalaprilat or placebo. Pressor responses to stepwise, incremental doses of angiotensin I were measured at 1 and 10 hours after dosing. The dose required to raise mean blood pressure by 20 mm Hg (PD20) was calculated individually, and the ratio of PD20 during enalaprilat to that during placebo (dose ratio, DR) was used for assessment of the extent of ACE inhibition. The pressor response was significantly attenuated at 1 hour after enalaprilat in both groups, but significant attenuation was evident at 10 hours after dose only in the II subjects. The DRs at both 1 hour (median, 5.43 versus 2.82, P=0.0035) and 10 hours (2.06 versus 0.84, P=0.0008) after enalaprilat were significantly higher in II subjects than in DD subjects.
The effect of enalaprilat was significantly greater and lasted longer in normotensive men homozygous for the II ACE genotype. By multivariate analysis, ACE (I/D) genotype and plasma angiotensin II levels were predictive of >50% of the variation in response to ACE inhibition.
我们研究了对比正常血压男性中ACE（I/D）基因不同基因型对血管紧张素转换酶抑制剂依那普利拉反应的可能影响。
DD型（n = 12）和II型（n = 11）ACE基因型的受试者接受依那普利拉或安慰剂静脉输注。给药后1小时和10小时测量对逐步递增剂量血管紧张素I的升压反应。分别计算使平均血压升高20 mmHg所需的剂量（PD20），并使用依那普利拉给药期间的PD20与安慰剂给药期间的PD20之比（剂量比，DR）来评估ACE抑制程度。两组在依那普利拉给药后1小时升压反应均显著减弱，但仅在II型受试者中给药后10小时有明显减弱。依那普利拉给药后1小时（中位数，5.43对2.82，P = 0.0035）和10小时（2.06对0.84，P = 0.0008）的DR在II型受试者中均显著高于DD型受试者。
依那普利拉对II型ACE基因型纯合的正常血压男性的作用显著更大且持续时间更长。通过多变量分析，ACE（I/D）基因型和血浆血管紧张素II水平可预测ACE抑制反应中>50%的变异性。
