Greefhorst A P, van Herwaarden C L
Eur J Clin Pharmacol. 1983;24(2):173-8. doi: 10.1007/BF00613813.
In 8 asthmatic patients a comparative study was performed of the ventilatory and haemodynamic effects of the beta 1-receptor stimulator prenalterol and the beta 2-receptor stimulator terbutaline infused in increasing doses after a placebo. Terbutaline caused a dose-dependent decrease in diastolic blood-pressure (BP) and an increase in systolic BP and heart-rate (HR), while mean arterial pressure (MAP) did not change. Prenalterol produced a dose-dependent increase in MAP and systolic BP, while diastolic BP was unaffected. HR was increased only by the largest dose of prenalterol. The haemodynamic effects of the terbutaline infusion can be explained by a reflex response to the vasodilatation induced by stimulation of the vascular beta 2-receptors, while the effects of prenalterol can mainly be accounted for by a direct action on beta 1-receptors in the heart. These observations show that the cardiac side-effects of beta 2-agonists cannot be avoided by producing more selective agonists. Terbutaline caused a dose-dependent increase in the ventilatory indices. Prenalterol in larger doses caused a limited but significant increase in the ventilatory indices, comparable to the decrease in ventilation caused by the beta 1-selective blocker metoprolol. These findings suggest that the ventilatory effects of metoprolol and prenalterol are mediated via beta 1-receptors in the airways, which apparently play a functional role in asthma.
对8名哮喘患者进行了一项对比研究,观察在给予安慰剂后,递增剂量静脉输注β1受体激动剂普瑞特罗和β2受体激动剂特布他林时的通气和血流动力学效应。特布他林可使舒张压(BP)呈剂量依赖性降低,收缩压和心率(HR)升高,而平均动脉压(MAP)无变化。普瑞特罗可使MAP和收缩压呈剂量依赖性升高,舒张压不受影响。仅在给予最大剂量普瑞特罗时心率才升高。输注特布他林的血流动力学效应可通过对血管β2受体刺激诱导的血管舒张的反射反应来解释,而普瑞特罗的效应主要可归因于对心脏β1受体的直接作用。这些观察结果表明,产生更具选择性的激动剂并不能避免β2激动剂的心脏副作用。特布他林可使通气指标呈剂量依赖性升高。较大剂量的普瑞特罗可使通气指标有有限但显著的升高,这与β1选择性阻滞剂美托洛尔引起的通气降低相当。这些发现提示,美托洛尔和普瑞特罗的通气效应是通过气道中的β1受体介导的,这些受体显然在哮喘中发挥功能性作用。