Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X
Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X
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DOI：
10.1016/s0002-9149(02)02664-4
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发表时间：
2002-11-01
影响因子：
2.8
通讯作者：
Chang, MS
中科院分区：
文献类型：
--
作者：
Chen, JW;Hsu, NW;Chang, MS
抑制血管紧张素转换酶(ACE)已被证明可以改善X综合征患者的临床心肌缺血(心绞痛、平板运动试验阳性、冠状动脉造影正常，没有证据表明I级冠状动脉痉挛)。为探讨长期应用血管紧张素转换酶(ACE)抑制剂对X综合征患者血管内皮细胞一氧化氮(NO)代谢及冠脉微血管功能的影响，将20例X综合征患者随机分为依那普利组(n=10)和安慰剂组(n=10)，每组10例。另有6名跑台运动试验阴性的年龄和性别匹配的受试者也被作为对照。与对照组相比，X综合征患者冠状动脉血流储备显著减少，血浆硝酸盐和亚硝酸盐水平降低，血浆L-精氨酸/不对称二甲基精氨酸比值(反映全身NO代谢的指标)降低，血管内皮功能降低。这些患者的血浆ADMA水平也升高，ADMA是一氧化氮合酶的内源性抑制物，von Willebrand因子是内皮损伤的标志。基线特征，包括运动能力和冠脉血流储备，依那普利组和安慰剂组相似。经过8周的治疗后，服用依那普利的患者运动时间(p=0.001)和冠脉流量储备(p=0.001)显著改善，而服用安慰剂的患者没有明显改善。依那普利治疗可降低血浆von Willebrand因子(p=0.03)和血浆ADMA水平(p=0.01)，升高NOx水平(p=0.01)和L-精氨酸/ADMA比值(p=0.01)，而不是安慰剂。
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 I 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 we're 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