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

心肌存在局部缓激肽-激肽系统，包括缓激肽(BK)-B_2受体，血管紧张素转换酶（ACE）抑制剂可使BK水平进一步升高。众所周知，ace抑制剂可能通过抑制BK的降解和/或通过增强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。作为一项初步研究，我们利用传统的微电极技术、膜片钳法和应变计研究了BK （10^<-7> ~ 10^<-5> M）对豚鼠心房和心室的心肌和酶分离的单细胞的动作电位、全膜电流和收缩的直接作用。在生理正常情况下，BK对豚鼠心室肌细胞的动作电位和膜电流的影响很小或没有变化。而BK能明显缩短经预处理后的动作电位持续时间，对心房和心室肌细胞均有显著影响。BK对心房肌细胞的影响较心室肌细胞更为明显，说明心房细胞BK- b_2受体密度高于心室细胞。据推测，当蛋白激酶A （PKA）被forskolin或β受体刺激完全激活时，BK发挥更有效的抑制作用，但在没有PKA激活的情况下，BK可能几乎没有作用（“拮抗增强”）。BK的作用方式似乎与乙酰胆碱非常相似。虽然BK不影响未受刺激细胞的基础Ca水平，但它可能会降低已经被福斯考林或β-刺激剂提高的细胞中的l型Ca电流（ICa），这是相当合理的。另一方面，关于BK对心室乳头肌收缩的作用，我们在实验中没有得到BK的特定作用。个体对BK应用的肌力反应变化很大，BK不时表现出双重作用。目前，我们无法解释这些发现。需要对这些问题进行进一步的研究，因为各种BK作用的可能机制仍有待确定。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