Gouin L, Cardinal R, Adam A, Drapeau G, Nadeau R
Faculté de médecine, Département de pharmacologie, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Québec, Canada.
J Cardiovasc Pharmacol. 1996 Aug;28(2):337-43. doi: 10.1097/00005344-199608000-00023.
Previous work has shown that, in rat ventricular muscle, bradykinin (BK) causes a dose-dependent increase in action potential duration (APD), an action that may be responsible for APD prolongation by captopril (kininase II). To determine which kinin receptor might be involved in APD prolongation, we studied the effects of B1- and B2-receptor agonists, as well as those of antagonists and mergepta (a kininase I inhibitor) added during BK superfusion. Action potentials were recorded by using the standard glass microelectrode technique in rat ventricular muscle preparations. Action-potential characteristics were compared between preparations superfused with peptide/drug-free Tyrode's solution (control group) and preparations superfused with peptide/drug-containing solution. APD was significantly longer in preparations superfused with BK (10(-8) M) than in the control group. The APD prolongation induced by BK, a known B2-receptor agonist, was significantly reduced by Hoe 140 (a B2 antagonist) and also by Lys[Leu8]des-Arg9-BK (a B1 antagonist), an action presumably related to inhibition of B1 receptor stimulation by the BK metabolite des-Arg9-BK. When mergepta was added in the presence of BK, APD prolongation by BK was significantly reduced, an effect that could have been related to reduced B1-receptor stimulation after inhibition of the endogenous generation of des-Arg9-BK by kininase I. Sar4-[d-Phe8]des-Arg9-BK, a B1-receptor agonist that is not degraded by kininase II, also prolonged APD. We conclude that both B1 and B2 receptors may be involved in APD prolongation induced in rat ventricular muscle preparations.
先前的研究表明，在大鼠心室肌中，缓激肽（BK）可使动作电位时程（APD）呈剂量依赖性增加，这一作用可能是卡托普利（激肽酶II）导致APD延长的原因。为了确定哪种激肽受体可能参与APD的延长，我们研究了B1和B2受体激动剂的作用，以及在BK灌流期间添加拮抗剂和甲丙脯氨酸（一种激肽酶I抑制剂）的作用。采用标准玻璃微电极技术记录大鼠心室肌标本的动作电位。比较用无肽/药物的台氏液灌流的标本（对照组）和用含肽/药物的溶液灌流的标本的动作电位特征。用BK（10(-8)M）灌流的标本的APD明显长于对照组。已知的B2受体激动剂BK诱导的APD延长被Hoe 140（一种B2拮抗剂）以及Lys[Leu8]des-Arg9-BK（一种B1拮抗剂）显著降低，这一作用可能与BK代谢产物des-Arg9-BK对B1受体刺激的抑制有关。当在BK存在的情况下添加甲丙脯氨酸时, BK诱导的APD延长显著降低，这一效应可能与激肽酶I抑制内源性des-Arg9-BK生成后B1受体刺激减少有关。Sar4-[d-Phe8]des-Arg9-BK，一种不会被激肽酶II降解的B1受体激动剂，也能延长APD。我们得出结论，B1和B2受体可能都参与了大鼠心室肌标本中诱导的APD延长。
