Kubli S, Feihl F, Waeber B
Division of Clinical Pathophysiology and Medical Teaching, University Hospital, Lausanne, Switzerland.
Clin Pharmacol Ther. 2001 Apr;69(4):238-44. doi: 10.1067/mcp.2001.114670.
Nebivolol is a selective beta(1)-adrenoceptor blocker that has a vasorelaxant activity thought to be the result of a facilitation of the release of nitric oxide from the endothelium. This study was undertaken in 12 healthy male volunteers to assess whether this compound increases the vasodilatory response to acetylcholine when administered orally at a dose commonly recommended for the treatment of cardiovascular diseases. The subjects were randomly allocated to an 8-day treatment with nebivolol (5 mg once a day) and atenolol (50 mg once a day) according to a cross-over design. The two treatments were separated by a 1-week washout period. On the first and the last day of each treatment phase, both before drug administration and 3 hours after drug administration, the forearm skin blood flow response to acetylcholine applied by iontophoresis was determined with the use of a laser Doppler scanner imaging system. The reactivity to acetylcholine was significantly increased 3 hours after the administration of nebivolol on both the first and the last day of treatment, whereas atenolol had no effect on this parameter. These data therefore indicate that nebivolol, but not atenolol, enhances the vasorelaxant activity of acetylcholine in the skin vascular bed; this is compatible with a facilitation by this beta-blocker of the endothelium-dependent vasodilation.
奈必洛尔是一种选择性β(1)-肾上腺素能受体阻滞剂,具有血管舒张活性,这种活性被认为是内皮细胞一氧化氮释放增加所致。本研究纳入了12名健康男性志愿者,旨在评估该化合物在以治疗心血管疾病的常用推荐剂量口服给药时,是否会增加对乙酰胆碱的血管舒张反应。受试者按照交叉设计随机分配接受为期8天的奈必洛尔(每日一次,每次5mg)和阿替洛尔(每日一次,每次50mg)治疗。两种治疗之间间隔1周的洗脱期。在每个治疗阶段的第一天和最后一天,在给药前和给药后3小时,使用激光多普勒扫描仪成像系统测定经离子导入法施加乙酰胆碱后前臂皮肤血流反应。在治疗的第一天和最后一天,给药后3小时,对乙酰胆碱的反应性在给予奈必洛尔后均显著增加,而阿替洛尔对该参数无影响。因此,这些数据表明,奈必洛尔而非阿替洛尔可增强皮肤血管床中乙酰胆碱的血管舒张活性;这与该β受体阻滞剂促进内皮依赖性血管舒张作用相符。