Mancini G B, Henry G C, Macaya C, O'Neill B J, Pucillo A L, Carere R G, Wargovich T J, Mudra H, Lüscher T F, Klibaner M I, Haber H E, Uprichard A C, Pepine C J, Pitt B
University of British Columbia, Vancouver, British Columbia, Canada.
Circulation. 1996 Aug 1;94(3):258-65. doi: 10.1161/01.cir.94.3.258.
Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized.
Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002).
TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.
血管紧张素转换酶（ACE）抑制剂可能通过改善内皮功能障碍，在高血压、充血性心力衰竭及急性心肌梗死的治疗中发挥某些有益作用。TREND（逆转内皮功能障碍试验）研究了喹那普利是否可改善无心力衰竭、心肌病或严重脂质异常的冠心病正常血压患者的内皮功能障碍，从而使影响内皮功能障碍的混杂变量降至最低。
采用双盲、随机、安慰剂对照设计，我们使用定量冠状动脉造影测量了喹那普利（每日40mg）对冠状动脉直径对乙酰胆碱反应的影响。主要反应变量是基线（随机分组前）和6个月随访血管造影之间目标节段乙酰胆碱诱发收缩的净变化。安慰剂组（n = 54）和喹那普利组（n = 51）在基线时对乙酰胆碱的收缩反应相当。6个月后，仅喹那普利组在对递增浓度乙酰胆碱的反应中显示出显著的净改善（在10(-6)mol/L时分别为4.5±3.0%[平均值±标准误]和-0.1±2.8%，在10(-4)mol/L时分别为12.1±3.0%和-0.8±2.9%，喹那普利组与安慰剂组相比；总体P = .002）。
TREND表明，喹那普利抑制ACE可改善正常血压且无严重高脂血症或心力衰竭证据患者的内皮功能障碍。ACE抑制的这些益处可能归因于血管紧张素II收缩效应和超氧化物生成效应的减弱，以及缓激肽分解减少继发的内皮细胞一氧化氮释放增强。
