Vandongen R, Margetts B, Deklerk N, Beilin L J, Rogers P
Br J Clin Pharmacol. 1986 Jun;21(6):627-32. doi: 10.1111/j.1365-2125.1986.tb05226.x.
This study re-examines the proposal that beta-adrenoceptor blockers with intrinsic sympathomimetic activity decrease plasma noradrenaline levels. Thirteen patients (aged 29-65 years) with uncomplicated essential hypertension were randomly allocated to a three period, double-blind cross-over trial. The treatment periods, each of 3 weeks duration, were composed of placebo, pindolol (5 mg twice daily) and metoprolol (100 mg twice daily), dispensed in identical capsules. At the end of each treatment period, patients were exercised on a bicycle ergometer to a predetermined workload. Blood pressure and heart rate were measured before, immediately on completion of exercise and after 10 min post-exercise rest. Blood samples for plasma noradrenaline and adrenaline determination were also collected at these times. Blood pressures were similar during treatment with pindolol and metoprolol. As expected, heart rate was consistently lower during metoprolol treatment. Basal, pre-exercise plasma noradrenaline and adrenaline were similar at the end of each treatment period. However, the increase following exercise was significantly greater during metoprolol treatment. The post-exercise increase during pindolol treatment was indistinguishable from that in the placebo period. These findings, in a randomised placebo-controlled study, therefore demonstrate that pindolol does not influence basal or exercise-stimulated plasma noradrenaline and adrenaline concentrations. This is best explained by a lack of effect of pindolol on the plasma clearance of catecholamines, which is impaired by beta-adrenoceptor blockers devoid of intrinsic sympathomimetic activity.
本研究重新审视了具有内在拟交感活性的β肾上腺素受体阻滞剂可降低血浆去甲肾上腺素水平这一观点。13例(年龄29 - 65岁)无并发症的原发性高血压患者被随机分配至一个为期三个阶段的双盲交叉试验。每个为期3周的治疗阶段分别为服用安慰剂、吲哚洛尔(每日两次,每次5mg)和美托洛尔(每日两次,每次100mg),药物装于相同胶囊中。在每个治疗阶段结束时,让患者在自行车测力计上运动至预定工作量。在运动前、运动结束即刻以及运动后休息10分钟后测量血压和心率。在这些时间点还采集血样用于测定血浆去甲肾上腺素和肾上腺素。在使用吲哚洛尔和美托洛尔治疗期间血压相似。正如预期的那样,在美托洛尔治疗期间心率持续较低。在每个治疗阶段结束时,基础、运动前的血浆去甲肾上腺素和肾上腺素水平相似。然而,在美托洛尔治疗期间运动后的升高明显更大。吲哚洛尔治疗期间运动后的升高与安慰剂阶段的升高无差异。因此,在一项随机安慰剂对照研究中的这些发现表明,吲哚洛尔不影响基础或运动刺激后的血浆去甲肾上腺素和肾上腺素浓度。这最好的解释是吲哚洛尔对儿茶酚胺的血浆清除率没有影响,而缺乏内在拟交感活性的β肾上腺素受体阻滞剂会损害儿茶酚胺的血浆清除率。