Lyons D, Webster J, Benjamin N
Clinical Age Research Unit, King's College School of Medicine & Dentistry, London, U.K.
Eur J Clin Pharmacol. 1997;51(5):373-8. doi: 10.1007/s002280050216.
Different ACE inhibitors can be distinguished in vitro by their affinity for converting enzyme in vascular and other tissues. Quinapril appears to be amongst the more effective inhibitors of vascular tissue ACE in vitro. This study assesses the in vivo effect of single oral doses of quinapril and enalapril, in attenuating the vasoconstrictive action of angiotensin I (AI) (which we have previously shown depends on its conversion to angiotensin II (AII) by vascular ACE) in the forearm resistance vessels of man.
The design was of randomized, open, placebo controlled, two way crossover type, Forearm blood flow (FABF) was measured simultaneously in both forearms by mercury in silastic strain gauge plethysmography. AI infusion were via a fine bore cannula in the left brachial artery with the right arm serving as a control.
Mean plasma ACE on placebo was 34.3 U.l-1. Both quinapril and enalapril produced a similar degree of plasma ACE inhibition reducing concentrations to 2.8 U.l-1 and 2.6 U.l-1 respectively. Quinapril caused a significantly greater inhibition of AI induced vasoconstriction with a 30.0% reduction compared with 67.0% and 85.0% for enalapril and placebo respectively. Enalapril attenuated AI induced vasoconstriction to a greater degree than placebo but the difference was not significantly different.
These results indicate that when quinapril and enalapril are administered as single 20 mg doses, each of which produces the same degree of plasma ACE inhibition and blood pressure reduction- quinapril inhibits vascular ACE to a greater degree than both enalapril and placebo.
不同的血管紧张素转换酶(ACE)抑制剂可通过其对血管及其他组织中转换酶的亲和力在体外加以区分。喹那普利在体外似乎是血管组织ACE更有效的抑制剂之一。本研究评估单次口服喹那普利和依那普利对人体前臂阻力血管中血管紧张素I(AI)(我们之前已表明其血管收缩作用依赖于血管ACE将其转化为血管紧张素II(AII))血管收缩作用的体内影响。
采用随机、开放、安慰剂对照、双向交叉设计。通过硅橡胶应变片汞柱式体积描记法同时测量双侧前臂的前臂血流量(FABF)。通过左肱动脉的细孔插管输注AI,右臂作为对照。
安慰剂组的平均血浆ACE为34.3 U·l⁻¹。喹那普利和依那普利均产生了相似程度的血浆ACE抑制作用,浓度分别降至2.8 U·l⁻¹和2.6 U·l⁻¹。喹那普利对AI诱导的血管收缩的抑制作用明显更强,降低了30.0%,而依那普利和安慰剂分别为67.0%和85.0%。依那普利对AI诱导的血管收缩的减弱程度大于安慰剂,但差异无统计学意义。
这些结果表明,当喹那普利和依那普利均以20 mg单剂量给药时,二者产生相同程度的血浆ACE抑制作用和血压降低效果——喹那普利对血管ACE的抑制作用比依那普利和安慰剂更强。