Thollon C, Bidouard J P, Cambarrat C, Delescluse I, Villeneuve N, Vanhoutte P M, Vilaine J P
Institut de Recherches Servier, Suresnes, France.
Circ Res. 1999 Mar 5;84(4):371-7. doi: 10.1161/01.res.84.4.371.
The present study was designed to test the ability of regenerated endothelium to evoke endothelium-dependent hyperpolarizations. Hyperpolarizations induced by serotonin and bradykinin were compared in isolated porcine coronary arteries with native or regenerated endothelium, 4 weeks after balloon endothelial denudation. The experiments were performed in the presence of inhibitors of nitric oxide synthase (Nomega-nitro-L-arginine) and cyclooxygenase (indomethacin). The transmembrane potential was measured using conventional glass microelectrodes. Smooth muscle cells from coronary arteries with regenerated endothelium were depolarized in comparison with control coronary arteries from the same hearts. Spontaneous membrane potential oscillations of small amplitude or spikes were observed in some of these arteries but never in arteries with native endothelium. In coronary arteries from control pigs, both serotonin and bradykinin induced concentration-dependent hyperpolarizations. In the presence of ketanserin, 10 micromol/L serotonin induced a transient hyperpolarization in control coronary arteries. Four weeks after balloon denudation, the response to serotonin was normal in arteries with native endothelium, but the hyperpolarization was significantly lower in coronary arteries with regenerated endothelium. In control arteries, the endothelium-dependent hyperpolarization obtained with bradykinin (30 nmol/L) was reproducible. Four weeks after balloon denudation, comparable hyperpolarizations were obtained in coronary arteries with native endothelium. By contrast, in arteries with regenerated endothelium, the hyperpolarization to bradykinin became voltage-dependent. In the most depolarized cells, the hyperpolarization to bradykinin was augmented. The changes in resting membrane potential and the alteration in endothelium-dependent hyperpolarizations observed in the coronary arteries with regenerated endothelium may contribute to the reduced response to serotonin and the unchanged relaxation to bradykinin described previously.
本研究旨在测试再生内皮引发内皮依赖性超极化的能力。在球囊内皮剥脱4周后，比较了具有天然或再生内皮的离体猪冠状动脉中由血清素和缓激肽诱导的超极化。实验在一氧化氮合酶抑制剂（Nω-硝基-L-精氨酸）和环氧化酶抑制剂（吲哚美辛）存在的情况下进行。使用传统玻璃微电极测量跨膜电位。与来自同一心脏的对照冠状动脉相比，具有再生内皮的冠状动脉中的平滑肌细胞发生了去极化。在其中一些动脉中观察到了小幅度的自发膜电位振荡或尖峰，但在具有天然内皮的动脉中从未观察到。在对照猪的冠状动脉中，血清素和缓激肽均诱导浓度依赖性超极化。在酮色林存在的情况下，10 μmol/L血清素在对照冠状动脉中诱导了短暂的超极化。球囊剥脱4周后，具有天然内皮的动脉对血清素的反应正常，但具有再生内皮的冠状动脉中的超极化明显较低。在对照动脉中，用缓激肽（30 nmol/L）获得的内皮依赖性超极化是可重复产生的。球囊剥脱4周后，具有天然内皮的冠状动脉中获得了类似的超极化。相比之下，在具有再生内皮的动脉中，对缓激肽的超极化变得依赖于电压。在去极化程度最高的细胞中，对缓激肽的超极化增强。在具有再生内皮的冠状动脉中观察到的静息膜电位变化和内皮依赖性超极化的改变可能导致先前描述的对血清素反应降低和对缓激肽舒张反应不变。
