Berkenboom G, Fontaine J, Desmet J M, Degre S
Cardiology Department, Erasmus Hospital, Brussels, Belgium.
Cardiovasc Res. 1987 Apr;21(4):299-304. doi: 10.1093/cvr/21.4.299.
Experiments were performed on canine and human isolated coronary arteries to characterise human coronary beta adrenoceptors and to determine whether or not beta blocking agents with different ancillary properties unmask the alpha adrenergic effect of noradrenaline in a similar way. The inhibitory effects of atenolol (a beta1 selective antagonist), epanolol (a beta1 selective antagonist with modest intrinsic sympathetic activity), and propranolol (a non-selective antagonist) were assessed on isoproterenol concentration-response curves. Regression analysis provided slopes not significantly different from unity and similar pA2 values for each agent in both preparations. In a second group of experiments, the effects of noradrenaline (10 mumol.litre-1) were assessed in the absence and presence of beta blockade. At equipotent doses (1 log or 2 log units from the pA2 values) each beta blocking agent unmasked the alpha effect of noradrenaline in the same way. This alpha effect of noradrenaline (10 mumol.litre-1) was completely abolished by prazosin 1 mumol.litre-1 in canine coronary arteries but only partially antagonised in human coronary arteries. Thus the property of a beta blocking agent to unmask the alpha adrenergic effect of adrenaline is mainly related to its affinity for the coronary smooth muscle beta adrenoceptors. These beta adrenoceptors were very similar in both preparations and appear to be mainly beta1. The alpha adrenoceptors seem, nevertheless, to be different and resistant to prazosin in human preparations.
对犬类和人类离体冠状动脉进行了实验，以表征人类冠状动脉β肾上腺素能受体，并确定具有不同辅助特性的β受体阻滞剂是否以类似方式揭示去甲肾上腺素的α肾上腺素能效应。评估了阿替洛尔（一种β1选择性拮抗剂）、依泮洛尔（一种具有适度内在交感活性的β1选择性拮抗剂）和普萘洛尔（一种非选择性拮抗剂）对异丙肾上腺素浓度-反应曲线的抑制作用。回归分析得出，两种制剂中每种药物的斜率与1无显著差异，且pA2值相似。在第二组实验中，评估了在不存在和存在β受体阻滞的情况下去甲肾上腺素（10 μmol·L-1）的作用。在等效剂量下（从pA2值起1个对数或2个对数单位），每种β受体阻滞剂以相同方式揭示了去甲肾上腺素的α效应。在犬冠状动脉中，1 μmol·L-1的哌唑嗪可完全消除去甲肾上腺素（10 μmol·L-1）的这种α效应，但在人类冠状动脉中仅部分拮抗。因此，β受体阻滞剂揭示肾上腺素α肾上腺素能效应的特性主要与其对冠状动脉平滑肌β肾上腺素能受体的亲和力有关。两种制剂中的这些β肾上腺素能受体非常相似，似乎主要是β1。然而，α肾上腺素能受体在人类制剂中似乎有所不同，且对哌唑嗪有抗性。
