Kocic I
Department of Pharmacology, Medical University of Gdansk, Poland.
J Pharm Pharmacol. 1998 Dec;50(12):1361-4. doi: 10.1111/j.2042-7158.1998.tb03360.x.
The aim of this study was to discover the effects of galanin, a neuropeptide comprising 29 amino acids capable of activating inward-rectifier K+ channels (IK1) in cardiomyocytes, on the force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and effective refractory period (ERP) of guinea-pig heart. The influence of galanin on the time-course of hypoxia-induced disturbances in contractility and ERP was also examined. Experiments were performed on the isolated right ventricle papillary muscle of guinea-pig heart. In the concentration range 0.001-0.01 microM, galanin had no significant effect on the measured parameters. At 0.03 and 0.1 microM, galanin exerted a positive inotropic action and prolonged ERP. Further increasing the concentration led to a negative inotropic action and significant shortening of ERP. Although simulated hypoxia induced a significant drop in Fc, +dF/dt and -dF/dt, and a significant shortening of ERP, recovery of all the measured parameters was complete after 10 min reperfusion. In the presence of 0.03 and 0.1 microM galanin the effect of hypoxia on the contractility of papillary muscle was more profound and reperfusion did not result in complete recovery. In contrast, addition of 1 microM galanin to the hypoxic solution significantly protected the muscle and recovery of the tissues during reperfusion was rapid and complete (in 5 min). One can conclude that galanin at lower concentrations induced a positive inotropic action and a prolongation of ERP, but increased the sensitivity of heart muscle to hypoxia. At higher concentrations however, galanin exerted a negative inotropic action but protected the muscle against hypoxia-induced disturbances in contractility.
本研究的目的是探究甘丙肽(一种由29个氨基酸组成的神经肽,能够激活心肌细胞内向整流钾通道(IK1))对豚鼠心脏收缩力(Fc)、收缩速度(+dF/dt)、舒张速度(-dF/dt)和有效不应期(ERP)的影响。还研究了甘丙肽对缺氧诱导的收缩性和ERP紊乱时间进程的影响。实验在豚鼠心脏分离的右心室乳头肌上进行。在0.001 - 0.01微摩尔浓度范围内,甘丙肽对所测参数无显著影响。在0.03和0.1微摩尔浓度时,甘丙肽发挥正性肌力作用并延长ERP。进一步增加浓度会导致负性肌力作用并显著缩短ERP。尽管模拟缺氧导致Fc、+dF/dt和 -dF/dt显著下降以及ERP显著缩短,但再灌注10分钟后所有测量参数完全恢复。在存在0.03和0.1微摩尔甘丙肽的情况下,缺氧对乳头肌收缩性的影响更显著,且再灌注未导致完全恢复。相反,向缺氧溶液中添加1微摩尔甘丙肽可显著保护心肌,再灌注期间组织恢复迅速且完全(5分钟内)。可以得出结论,较低浓度的甘丙肽诱导正性肌力作用并延长ERP,但增加了心肌对缺氧的敏感性。然而,较高浓度的甘丙肽发挥负性肌力作用,但保护心肌免受缺氧诱导的收缩性紊乱影响。