Koh K K, Bui M N, Hathaway L, Csako G, Waclawiw M A, Panza J A, Cannon R O
Cardiology Branch and the Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
Am J Cardiol. 1999 Feb 1;83(3):327-31. doi: 10.1016/s0002-9149(98)00862-5.
Angiotensin-converting enzyme (ACE) inhibition has been shown to improve endothelium-dependent vasodilator responsiveness, but the contribution and mechanism of enhanced nitric oxide (NO) bioactivity to this effect in patients with coronary artery disease are unknown. We investigated the effect of ACE inhibition on brachial artery dilator responsiveness to increased shear stress after forearm ischemia by ultrasonography as a bioassay for endothelial NO available to vascular smooth muscle in 9 men with coronary artery disease. Serum nitrogen oxides were measured after 3 days of nitrate-restricted diet as an index of endothelial NO release. Patients received quinapril 20 to 40 mg/day for 8 weeks. Relative to pretreatment measurements, quinapril increased flow-mediated dilation (from 2.4+/-0.4 to 10.8+/-2.2, p <0.001), with significant improvement persisting 1 week after discontinuation of therapy (6.7+/-2.5%, p <0.01). However, quinapril decreased serum nitrogen oxide levels by 19+/-17% compared with pretreatment values (from 58.2+/-19.0 to 46.0+/-13.3 micromol/L, p <0.01). Thus, ACE inhibitor therapy with quinapril selectively improves endothelium-dependent vasodilator responsiveness by increased NO bioactivity in relation to vascular smooth muscle in patients with coronary artery disease, an effect achieved at a lower rate of NO release from the endothelium. These findings suggest that ACE inhibitors may reduce angiotensin II-induced oxidant stress within the vessel wall and protect NO from oxidative inactivation. This effect may reduce endothelial NO synthesis required for vasomotor regulation.
血管紧张素转换酶（ACE）抑制已被证明可改善内皮依赖性血管舒张反应，但在冠心病患者中，一氧化氮（NO）生物活性增强对这种效应的作用及机制尚不清楚。我们通过超声检查，对9名冠心病男性患者进行了前臂缺血后肱动脉对剪切应力增加的舒张反应的ACE抑制作用研究，以此作为血管平滑肌可利用的内皮NO的生物测定方法。在进行3天硝酸盐限制饮食后，测量血清氮氧化物作为内皮NO释放的指标。患者接受喹那普利20至40毫克/天，持续8周。与治疗前测量值相比，喹那普利增加了血流介导的舒张（从2.4±0.4增加到10.8±2.2，p<0.001），停药1周后仍有显著改善（6.7±2.5%，p<0.01）。然而，与治疗前值相比，喹那普利使血清氮氧化物水平降低了19±17%（从58.2±19.0降至46.0±13.3微摩尔/升，p<0.01）。因此，在冠心病患者中，喹那普利的ACE抑制剂治疗通过增加与血管平滑肌相关的NO生物活性，选择性地改善了内皮依赖性血管舒张反应，这一效应是在较低的内皮NO释放率下实现的。这些发现表明，ACE抑制剂可能会降低血管壁内血管紧张素II诱导的氧化应激，并保护NO免受氧化失活。这种效应可能会减少血管舒缩调节所需的内皮NO合成。
