Forster C, Larosa G, Armstrong P W
Department of Medicine, University of Toronto, St. Michael's Hospital, Ont. Canada.
Can J Physiol Pharmacol. 1992 Oct;70(10):1417-22. doi: 10.1139/y92-199.
In vitro coronary artery responsiveness to angiotensin I, angiotensin II, noradrenaline, phenylephrine, BHT 920, and potassium chloride together with functional relaxation to acetylcholine was investigated in dogs with pacing-induced heart failure treated with enalapril (oral administration of 10 mg.day-1) for a mean duration of 26 days. Although maximal responses generated to both angiotensin I and angiotensin II were unaltered in the enalapril-treated group, angiotensin II became more potent following enalapril treatment: the EC50 for angiotensin II following placebo treatment was 2.4 (0.6-5.8; 95% confidence limits) nM and following enalapril treatment was 0.03 (0.007-0.1; 95% confidence limits) nM. In addition to the above changes, coronary artery rings from dogs treated with enalapril developed significantly less tension to noradrenaline, phenylephrine, and BHT 920. In contrast, responses to potassium chloride were unaltered following enalapril treatment. However, the relaxation to acetylcholine was enhanced from 38.9 +/- 3.0 to 50.4 +/- 3.5% (placebo versus enalapril, p < 0.05). These findings indicate that enalapril may possess alpha-blocking properties and enhance the relaxation response to acetylcholine through an endothelial-dependent mechanism in addition to inhibiting converting enzyme.
在平均治疗时长为26天、接受依那普利（口服剂量为10毫克/天）治疗的起搏诱导型心力衰竭犬中，研究了体外冠状动脉对血管紧张素I、血管紧张素II、去甲肾上腺素、去氧肾上腺素、BHT 920和氯化钾的反应以及对乙酰胆碱的功能性舒张反应。虽然依那普利治疗组对血管紧张素I和血管紧张素II产生的最大反应未改变，但依那普利治疗后血管紧张素II的效力增强：安慰剂治疗后血管紧张素II的半数有效浓度（EC50）为2.4（0.6 - 5.8；95%置信区间）纳摩尔，依那普利治疗后为0.03（0.007 - 0.1；95%置信区间）纳摩尔。除上述变化外，依那普利治疗犬的冠状动脉环对去甲肾上腺素、去氧肾上腺素和BHT 920产生的张力显著降低。相比之下，依那普利治疗后对氯化钾的反应未改变。然而，对乙酰胆碱的舒张反应从38.9±3.0%增强至50.4±3.5%（安慰剂组与依那普利组相比，p<0.05）。这些发现表明，依那普利除抑制转化酶外，可能还具有α阻断特性，并通过内皮依赖性机制增强对乙酰胆碱的舒张反应。
