Brown J D, Brown M E
J Pharmacol Exp Ther. 1977 Jan;200(1):166-73.
The effect of tolbutamide on contractility and the concentration of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in ventricular muscle was examined in the intact beating rat heart. The hearts were perfused in a nonrecirculated (Langendorff) fashion. Bolus injections of tolbutamide caused an increase in cardiac contractility. This increase in contractility was markedly inhibited when bovine albumin (3 g/100 ml) was present in the perfusing fluid. The increase in contractility caused by tolbutamide was not preceded by or associated with any change in the concentration of cyclic AMP in the ventricular muscle. Further studies utilizing a simultaneous injection of norepinephrine and tolbutamide demonstrated no significant effect of this combination on the concentration of cardiac cylcic AMP produced by an injection of norepinephrine alone. Our findings suggest that in the intact beating rat heart the positive inotropic effect of tolbutamide is not mediated via an increase in the concentration of cardiac cyclic AMP and that tolbutamide does not significantly potentiate the effect of catecholamines on cardiac cyclic AMP concentration.
在完整跳动的大鼠心脏中，研究了甲苯磺丁脲对心室肌收缩力和环磷酸腺苷（cAMP）浓度的影响。心脏以非循环（Langendorff）方式灌注。静脉推注甲苯磺丁脲可使心脏收缩力增强。当灌注液中存在牛血清白蛋白（3 g/100 ml）时，这种收缩力的增强受到显著抑制。甲苯磺丁脲引起的收缩力增强之前或与心室肌中cAMP浓度的任何变化均无关联。进一步利用同时注射去甲肾上腺素和甲苯磺丁脲的研究表明，这种组合对单独注射去甲肾上腺素所产生的心脏cAMP浓度没有显著影响。我们的研究结果表明，在完整跳动的大鼠心脏中，甲苯磺丁脲的正性肌力作用不是通过增加心脏cAMP浓度介导的，并且甲苯磺丁脲不会显著增强儿茶酚胺对心脏cAMP浓度的影响。
