ENDOTHELIUM DEPENDENT VASODILATION RESPONSE--ACE INHIBITOR IN CORONARY DISEASE

动脉粥样硬化的动物模型显示， 氧化脂蛋白和自由基分子氧化一氧化氮 (NO)转化为生物惰性或有毒分子， 降低NO的生物活性。为了确定 血管紧张素转换酶（ACE）介导 冠状动脉内皮依赖性舒张功能的改善 动脉疾病（CAD），我们每天服用喹那普利20-40 mg， 9例CAD男性患者8周，测量肱动脉 前臂缺血后血流介导的扩张（FMD）， 血清NO2/NO3在3天的无氮饮食。我们还测量 硝酸甘油（TNG）后内皮非依赖性舒张。数据 =平均值+/- SD。在喹那普利治疗时，FMD增加至 10.8+/-2.2%，较基线值2.4+/-0.4%（p<0.001）：1 治疗后一周FMD下降至6.7 ± 2.5%。应对 硝酸甘油在基线时与喹那普利相似（12.5 ± 2.8%）， (14.1+/-3.4%）和停药1周（13.7+/-2.9%）。血清 一氧化氮在喹那普利治疗后下降（46.0+/-13.3 microM） 与基线值（58.2+/-19.0 microM，p<0.02）相比， 停药一周后水平增加至56.1+/-14.8 microM。 喹那普利8周后FMD显著改善 治疗伴随着减少管腔释放的NO 进入血液这些数据表明，ACE抑制剂可能 减少血管壁内血管紧张素II诱导的氧化应激， 保护NO不被氧化。减少NO降解， 反过来可能会降低血管扩张所需的NO合成速率 调控我们的结论是ACE抑制剂治疗可以改善NO 具有增强的内皮依赖性血管扩张剂的生物活性 这是在较低的NO合成速率下完成的。

Animal models of atherosclerosis have shown that oxidized lipoproteins and free radical molecules oxidize nitric oxide (NO) into biologically inert or toxic molecules, with the net effect of reduced NO bioactivity. In order to determine the mechanism of angiotensin converting enzyme (ACE) inhibitor-mediated mprovement in endothelium-dependent vasodilation in coronary artery disease (CAD), we administered quinapril 20-40 mg daily for 8 weeks to 9 men with CAD, with measures of brachial artery flow-mediated dilation (FMD) following forearm ischemia and serum NO2/NO3 on a 3-day nitrogen-free diet. We also measured endothelium- independent dilation after nitroglycerin (TNG). Data = mean +/- SD. On quinapril therapy, FMD increased to 10.8+/-2.2% from a baseline value of 2.4+/-0.4% (p<0.001): one week after therapy FMD declined to 6.7+/-2.5%. The response to nitroglycerin was similar at baseline (12.5+/-2.8%), on quinapril (14.1+/-3.4%), and one week off therapy (13.7+/-2.9%). Serum nitrogen oxide declined on quinapril therapy (46.0+/-13.3 microM) compared with baseline values (58.2+/-19.0 microM, p<0.02); one week off therapy levels had increased to 56.1+/-14.8 microM. Significant improvement in FMD following 8 weeks of quinapril therapy was accompanied by reduction in the luminal release of NO into the bloodstream. These data suggest that ACE inhibitors may reduce angiotensin II-induced oxidant stress within the vessel wall, with protection of NO from oxidation. Reduced NO degradation in turn may reduce the rate of NO synthesis required for vasomotor regulation. We conclude that ACE inhibitor therapy improves NO bioactivity with enhanced endothelium-dependent vasodilator responsiveness that is accomplished at a lower rate of NO synthesis.