Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure.
Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure.
复制标题
喹那普利拉和依那普利拉对慢性心力衰竭患者导管动脉内皮功能的不同影响。
作者：
Burkhard Hornig;Naoshi Arakawa;Daniel Haussmann;Helmut Drexler
背景
慢性心力衰竭（CHF）与内皮功能障碍相关，包括血流依赖性（内皮介导）舒张功能受损（FDD）。我们先前已经证明，ACE抑制剂改善健康志愿者内皮介导的血管舒张。本研究旨在确定ACE抑制剂是否改善CHF患者受损的FDD。因为它们对组织ACE的亲和力可能影响ACE抑制剂影响内皮功能的能力，我们比较了喹那普利拉（对组织ACE的高亲和力）和依那普利拉（对组织ACE的低亲和力）对CHF患者FDD的影响。
方法和结果
采用高分辨率超声和多普勒测量CHF患者桡动脉直径和血流。在静息和反应性充血（引起内皮介导的扩张）期间，在N-单甲基-L-精氨酸（L-NMMA）抑制内皮细胞一氧化氮合成之前和之后，测定了喹那普利拉1.6 μ g/min（n = 15）和依那普利拉5 μ g/min（n=15）的动脉内输注的作用。奎那普利拉使FDD改善>40%（10.2+/-0.6%与6.9+/-0.6%; P<0.01），而依那普利拉则没有影响。特别是，喹那普利拉使一氧化氮介导的FDD部分（即L-NMMA抑制）增加>100%（5.6+/-0.5% vs 2.5+/-0.5%; P<0.01）。依那普利拉即使以相同剂量（5 μ g/min）输注两次和高达30 μ g/min，对FDD也没有影响。硝普钠对桡动脉直径和血流的影响在接受喹那普利拉、依那普利拉和安慰剂治疗的患者中相似。
结论
喹那普利拉可通过增加一氧化氮的利用率改善CHF患者的FDD，而依那普利拉则不然。这一观察结果表明，喹那普利拉和依那普利拉之间存在内在差异，决定了改善内皮介导的血管舒张的能力，即它们对组织ACE的不同亲和力。
BACKGROUND
Chronic heart failure (CHF) is associated with endothelial dysfunction, including impaired flow-dependent (endothelium-mediated) dilation (FDD). We have previously shown that ACE inhibition improves endothelium-mediated vasodilation in healthy volunteers. The present study was designed to determine whether ACE inhibition improves the impaired FDD in patients with CHF. Because their affinity to tissue ACE may influence the ability of ACE inhibitors to affect endothelial function, we compared the effects of quinaprilat (high affinity to tissue ACE) and enalaprilat (low affinity to tissue ACE) on FDD in patients with CHF.
METHODS AND RESULTS
High-resolution ultrasound and Doppler were used to measure radial artery diameter and blood flow in patients with CHF. The effects of intra-arterial infusion of quinaprilat 1.6 microg/min (n=15) and enalaprilat 5 microg/min (n=15) were determined at rest and during reactive hyperemia (causing endothelium-mediated dilation) before and after N-monomethyl-L-arginine (L-NMMA) to inhibit endothelial synthesis of nitric oxide. Quinaprilat improved FDD by >40% (10.2+/-0.6% versus 6.9+/-0.6%; P<0.01), whereas enalaprilat had no effect. In particular, the part of FDD mediated by nitric oxide (ie, inhibited by L-NMMA) was increased by >100% with quinaprilat (5.6+/-0.5% versus 2.5+/-0.5%; P<0.01). Enalaprilat had no effect on FDD even when it was infused twice in the same dose (5 microg/min) and up to 30 microg/min. The effect of sodium nitroprusside on radial artery diameter and blood flow was similar in patients treated with quinaprilat, enalaprilat, and placebo.
CONCLUSIONS
Quinaprilat improves FDD in patients with CHF as the result of increased availability of nitric oxide, whereas enalaprilat does not. This observation suggests that intrinsic differences exist between quinaprilat and enalaprilat that determine the ability to improve endothelium-mediated vasodilation, ie, their different affinity to tissue ACE.
激肽和内皮依赖性松弛对灌注犬动脉中的转化酶抑制剂的影响。
影响因子：
3
作者：
Mombouli,JV;Vanhoutte,PM
通讯作者：
Vanhoutte,PM
影响因子：
20.1
作者：
Carolyn J. Smith;Dong Sun;C. Hoegler;Barrie S. Roth;Xiaoping Zhang;Gong Zhao;Xiaobin Xu;Y. Kobari
通讯作者：
Carolyn J. Smith;Dong Sun;C. Hoegler;Barrie S. Roth;Xiaoping Zhang;Gong Zhao;Xiaobin Xu;Y. Kobari
影响因子：
20.1
作者：
MOMBOULI, JV;ILLIANO, S;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM