Effect of bradykinin on excitation-contraction coupling in excised human atrial muscles

心肌具有局部激肽释放酶-激肽系统，包括缓激肽(BK)-B_2受体，血管紧张素转换酶(ACE)抑制剂可进一步增加BK的水平。已知ACE抑制剂可能通过抑制BK的降解和/或增强BK的药理作用来提供心脏保护。然而，BK对心肌细胞的直接作用尚不明确。作为初步研究，我们用常规微电极技术、膜片钳技术和应变计研究了BK(10^&lt；-7；-5&gt；M)对豚鼠心肌和酶分离的单个豚鼠心房和心室肌细胞动作电位、全耳膜电流和收缩的直接作用。而BK可明显缩短…的动作电位时程，延长动作电位时程心房和心室肌细胞均较多。BK的这些作用在心房肌细胞中比在心室肌细胞中更明显，提示心房细胞比心室细胞具有更高的BK-B_2受体密度。当蛋白激酶A(PKA)被Forsklin或β受体刺激完全激活时，BK可能发挥更强的抑制作用，但在没有PKA激活的情况下，BK可能几乎没有作用。BK的作用模式似乎与乙酰胆碱非常相似。在已经被Forskoline或β激动剂升高的细胞中，BK可能会降低ICa)，尽管它不影响未刺激细胞的基础ICa水平。另一方面，关于BK对心室乳头肌收缩的影响，我们在实验中没有得到BK的特定作用。个体对BK的肌力反应差异很大，BK有时表现出双重作用。目前，我们还没有对这些发现做出解释。这些问题还需要进一步的研究，因为BK各种作用的可能机制仍有待确定。较少

The myocardium has a local kallikrein-kinin system including bradykinin(BK)-B_2 receptors, and the level of BK is further increased by angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE-inhibitor may provide cardioprotection by inhibiting the degradation of BK and/or by potentiating the pharmacological actions of BK. However, direct effect of BK on myocardial cells is as yet equivocal. As a pilot study, we have investigated the direct actions of BK (10^<-7>〜10^<-5> M) on action potentials, whole-eell membrane currents, and contraction in cardiac muscles and enzymatically-isolated single cells of guinea-pig atria and ventricle, using conventional microelectrode technique, patch clamp method and strain gauge.BK was, under physiologically-normal condition, shown to produce minimal or no changes in action potentials and membrane currents of guinea-pig ventricular myocytes. However, BK markedly shortened action potential duration prolonged by pretreatment with forskol in in … More both atrial and ventricular myocytes. These effects of BK were more pronounced in atrial myocytes as compared with ventricular ones, suggesting that atrial cell has higher density of BK-B_2 receptor than ventricular cell.It is assumed that BK exerts its more potent inhibitory action when the protein kinase A )PKA) is fully activated by an application of forskolin or β-receptor stimulation, but BK may have little or no effect under condition without PKA activation )"accentuated antagonism"). The mode of action of BK appears to be quite similar to that of acetylcholine. It is quite plausible that BK may reduce L-type Ca current )ICa) in cells where it has already been raised by forskoline or β-stimulants, though it does not affect the basal level of ICa in unstimulated cells. On the other hand, in regard to the effect of BK on the contraction in ventricular papillary muscle, we could not obtain the specified effects of BK in our experiments. Individual inotropic responses to BK application were quite variable, and BK showed dual action from time to time. At present, we have no explanation of the findings.Further studies into these problems are needed because the possible mechanisms underlying various BK's actions remain to be determined. Less