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首页> 外文期刊>Molecular and Cellular Biochemistry: An International Journal for Chemical Biology >Effects of glyburide (glibenclamide) on myocardial function in Langendorff perfused rabbit heart and on myocardial contractility and slow calcium current in guinea-pig single myocytes
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Effects of glyburide (glibenclamide) on myocardial function in Langendorff perfused rabbit heart and on myocardial contractility and slow calcium current in guinea-pig single myocytes

机译：格列本脲（格列本脲）对Langendorff灌注兔心脏的心肌功能以及对豚鼠单个肌细胞的心肌收缩力和慢钙电流的影响

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摘要

Glyburide, also known as glibenclamide, was shown to have positive inotropic effect in human and animal hearts. The objectives of the present study was to investigate the effects of glyburide on developed left ventricular pressure (DLVP), coronary flow (CF), and heart rate (HR), in isolated rabbit heart as well as its effects on myocardial contractility and L-type calcium current, i_(Ca,) in guinea pig myocytes. Rabbit hearts were mounted on Langendorff apparatus and perfused with an oxygenated Krebs for 30 min until reaching steady state to be followed by 20 min of experimental perfusion divided into 5 min of control perfusion and 15 min of perfusion with Glyburide (10 μM). Ventricular myocytes were isolated by enzymatic dispersion technique and superfused in an oxygenated Tyrode solution. Cells were voltage-clamped at holding potential-40 mV to inactivate Na~+ current and a step depolarizations, 200 msec duration, to 0 mV was applied to elicit i_(Ca). The contractions of the myocytes were measured by optical methods. Glyburide significantly increased DLVP by 30% and CF by 36% but had no effect on HR. Glyburide increased cell contractility by 7 ± 6, 18 ± 7, 28 ± 9 and 54 ± 15% for 0,1 1, 10 and 100 μM respectively, P < 0.001. Meanwhile it depressed i_(Ca) by 9 ± 6 and 19 ± 8% for 1 and 10 μM respectively. In conclusion, glyburide increased contractility of guinea pig single myocytes and of isolated rabbit heart, as indicated by increased developed left ventricular pressure while it depressed i_(Ca). It is hypothesized that an elevation in intracellular calcium, which caused increased myocardial contractility, could be attributed to an increase in intracellular Na~+ that could increase intracellular calcium via Na~+/Ca~(2+) exchange.
机译：格列本脲，也称为格列本脲，已显示对人和动物心脏具有正性肌力作用。本研究的目的是研究格列本脲对离体兔心脏发达的左心室压力（DLVP），冠状动脉血流（CF）和心率（HR）的影响，以及其对心肌收缩力和L-豚鼠心肌细胞中的钙电流类型i_（Ca）。将兔心脏安装在Langendorff仪器上，并用充氧的Krebs灌注30分钟直至达到稳态，然后进行20分钟的实验灌注，分为5分钟的对照灌注和15分钟的格列本脲（10μM）灌注。通过酶分散技术分离心室肌细胞，并在氧化的Tyrode溶液中进行融合。将细胞钳位在保持电位为40 mV的电压上，以灭活Na +电流，并以200毫秒的持续时间去极化至0 mV进行逐步去极化，以诱发i_（Ca）。通过光学方法测量心肌细胞的收缩。格列本脲显着增加DLVP 30％和CF 36％，但对HR无影响。格列本脲对于0.1、1、10和100μM的细胞收缩力分别提高了7±6、18±7、28±9和54±15％，P <0.001。同时，对于1和10μM，i_（Ca）分别降低了9±6和19±8％。总之，格列本脲增加了豚鼠单肌细胞和离体兔心脏的收缩力，这表现为在i_（Ca）降低时左心室压力升高。据推测，引起心肌收缩力增加的细胞内钙的升高可归因于细胞内Na +的增加，其可通过Na〜+ / Ca〜（2+）交换增加细胞内钙的含量。

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