Chen Jaw-Wen, Hsu Nai-Wei, Wu Tao-Cheng, Lin Shing-Jong, Chang Mau-Song
Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Am J Cardiol. 2002 Nov 1;90(9):974-82. doi: 10.1016/s0002-9149(02)02664-4.
Angiotensin-converting enzyme (ACE) inhibition has been shown to improve clinical myocardial ischemia in patients with syndrome X (angina pectoris, positive treadmill exercise test, normal coronary angiograms, and no evidence of coronary spasm). This study was conducted to investigate the effects of long-term ACE inhibitors on endothelial nitric oxide (NO) metabolism and coronary microvascular function in patients with syndrome X. After a 2-week washout period, 20 patients with syndrome X were randomized to receive either enalapril, an ACE inhibitor, 5 mg twice daily (n = 10) or placebo (n = 10) in a double-blind design for 8 weeks. Another 6 age- and gender-matched subjects with negative treadmill exercise tests were also studied as controls. Compared with control subjects, patients with syndrome X had significantly reduced coronary flow reserve, reduced plasma levels of nitrate and nitrite (NOx), and a reduced plasma L-arginine to asymmetric dimethylarginine (ADMA) ratio (an index of systemic NO metabolism), as well as reduced endothelial function. These patients also had increased plasma levels of ADMA, which is an endogenous inhibitor of NO synthase and of von Willebrand factor, a marker of endothelial injury. Baseline characteristics including exercise performance and coronary flow reserve were similar between enalapril and placebo groups. After an 8-week treatment period, exercise duration (p = 0.001) and coronary flow reserve (p = 0.001) significantly improved with enalapril but not with placebo. Enalapril treatment, but not placebo, reduced plasma von Willebrand factor (p = 0.03) and ADMA levels (p = 0.01) and increased NOx levels (p = 0.01) and the ratio of L-arginine to ADMA (p <0.01). In patients with syndrome X, the plasma NOx level was positively and ADMA level inversely correlated with coronary flow reserve before and after the treatment. In conclusion, long-term ACE inhibitor treatment with enalapril improved coronary microvascular function as well as myocardial ischemia in patients with syndrome X. This may be related to the improvement of endothelial NO bioavailability with the reduction of plasma ADMA levels.
血管紧张素转换酶（ACE）抑制已被证明可改善X综合征（心绞痛、平板运动试验阳性、冠状动脉造影正常且无冠状动脉痉挛证据）患者的临床心肌缺血情况。本研究旨在探讨长期使用ACE抑制剂对X综合征患者内皮型一氧化氮（NO）代谢及冠状动脉微血管功能的影响。经过2周的洗脱期后，20例X综合征患者被随机分为两组，采用双盲设计，一组每日两次服用5 mg依那普利（一种ACE抑制剂，n = 10），另一组服用安慰剂（n = 10），为期8周。另外6例年龄和性别匹配且平板运动试验阴性的受试者作为对照进行研究。与对照受试者相比，X综合征患者的冠状动脉血流储备显著降低，血浆硝酸盐和亚硝酸盐（NOx）水平降低，血浆L-精氨酸与不对称二甲基精氨酸（ADMA）的比值（全身NO代谢指标）降低，内皮功能也降低。这些患者的血浆ADMA水平也升高，ADMA是NO合酶的内源性抑制剂，也是内皮损伤标志物血管性血友病因子的抑制剂。依那普利组和安慰剂组的基线特征（包括运动能力和冠状动脉血流储备）相似。经过8周的治疗期后，依那普利治疗可使运动持续时间（p = 0.001）和冠状动脉血流储备（p = 0.001）显著改善，而安慰剂组则无此效果。依那普利治疗可降低血浆血管性血友病因子（p = 0.03）和ADMA水平（p = 0.01），并提高NOx水平（p = 0.01）以及L-精氨酸与ADMA的比值（p <0.01），而安慰剂则无此作用。在X综合征患者中，治疗前后血浆NOx水平与冠状动脉血流储备呈正相关，ADMA水平与冠状动脉血流储备呈负相关。总之，长期使用依那普利进行ACE抑制剂治疗可改善X综合征患者的冠状动脉微血管功能以及心肌缺血情况。这可能与血浆ADMA水平降低导致内皮型NO生物利用度提高有关。
