Satoh H, Matsui K
Department of Pharmacology, Nara Medical University, Japan.
J Pharm Pharmacol. 1997 May;49(5):505-10. doi: 10.1111/j.2042-7158.1997.tb06832.x.
The effects of free-radical generating systems and angiotensin-converting enzyme (ACE) inhibitors on the action potentials and contractile force in guinea-pig cardiac muscles were examined using conventional microelectrode and whole-cell voltage-clamp methods at 36 degrees C. Hydrogen peroxide (30-100 microM) prolonged 50%, 75% and 90% repolarization of action-potential duration (APD) approximately 15-25 min after its application. But the longer exposure reversed the APD shortening in a concentration-dependent manner. Other action-potential parameters were not altered to a significant extent. The contractile force was increased. Longer exposure inhibited the enhanced force (but it was still larger than control). The effects on the spontaneous action potential from right atrial muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100 microM) inhibited L-type Ca2+ current and enhanced delayed rectifier K+ current. The effects of light-activated rose bengal (10-100 nM) on the APD were similar to, but more potent than, those of H2O2. The response was observed rapidly after a light illumination. During exposure to rose bengal (100 nM), abnormal spontaneous action potentials or arrhythmias such as a bigeminy occurred, presumably because of early and delayed afterdepolarizations. The responses were irreversible. At 300 microM ACE inhibitors, captopril and enalapril, protected the changes induced by these free radicals. These results indicate that H2O2 has a dual, time-dependent, action on the APD and rose bengal with light illumination produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i and then cellular Ca2+ overload occurred. These responses were protected by ACE inhibitors.
在36℃下，使用传统微电极和全细胞膜片钳方法，研究了自由基生成系统和血管紧张素转换酶（ACE）抑制剂对豚鼠心肌动作电位和收缩力的影响。过氧化氢（30 - 100μM）在应用后约15 - 25分钟使动作电位时程（APD）的50%、75%和90%复极化延长约15 - 25分钟。但较长时间暴露以浓度依赖的方式使APD缩短逆转。其他动作电位参数没有显著改变。收缩力增加。较长时间暴露会抑制增强的收缩力（但仍大于对照组）。对右心房肌自发动作电位的影响几乎相同。在全细胞膜片钳实验中，H2O2（100μM）抑制L型钙电流并增强延迟整流钾电流。光激活的孟加拉玫瑰红（10 - 100 nM）对APD的影响与H2O2相似，但更有效。光照后迅速观察到反应。在暴露于孟加拉玫瑰红（100 nM）期间，出现异常自发动作电位或心律失常，如二联律，可能是由于早期和延迟后去极化。这些反应是不可逆的。在300μM时，ACE抑制剂卡托普利和依那普利可保护这些自由基诱导的变化。这些结果表明，H2O2对APD具有双重、时间依赖性作用，光照下的孟加拉玫瑰红能迅速产生反应。氧衍生自由基增加[Ca]i，随后发生细胞钙超载。这些反应受到ACE抑制剂的保护。
