Neubauer S, Ertl G, Pulzer F, Haas U, Hirsch A, Zimmermann S, Kochsiek K
Medizinische Universitätsklinik, Würzburg, F.R.G.
J Cardiovasc Pharmacol. 1990 Nov;16(5):804-11. doi: 10.1097/00005344-199011000-00017.
We examined the effects of the vasoconstrictor peptide endothelin-1 in isolated hearts under ischemic and cardioplegic conditions. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. Cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol in four groups of hearts. Coronary flow decreased with increasing dosages and was almost abolished at 400 pmol in control hearts perfused at a constant pressure of 100 mm Hg. In hearts made ischemic by reducing coronary perfusion pressure to 35 mm Hg, thus reducing coronary flow by 76%, the constrictor effect of endothelin-1 was well preserved. The endothelin-1 dose-response curve was unaltered when hearts were perfused with buffer containing 30 mM KCl to abolish mechanical activity without reducing extracellular Ca2+ concentration. A fourth group of hearts was perfused with Ca2(+)-free buffer, thus eliminating the source of extracellular Ca2+ as well as mechanical activity. In this group, the constrictor response to endothelin-1 was largely, but not completely, abolished, with a maximal constrictor effect of only 19% as opposed to 87% in control hearts. We conclude that in isolated rat heart endothelin-1 is a potent coronary constrictor under ischemic perfusion conditions and that absence of mechanical activity does not affect the action of endothelin-1, for which the presence of extracellular Ca2+ is essential. The small residual constrictor response with Ca2(+)-free perfusion is probably due to release of Ca2+ from intracellular stores.
我们研究了血管收缩肽内皮素 -1在缺血和心脏停搏条件下对离体心脏的影响。将离体等容大鼠心脏在恒压下用 Krebs-Henseleit 缓冲液灌注。在四组心脏中，获得了 0.04 - 400 pmol 内皮素 -1 推注的累积剂量 - 反应曲线。在 100 mmHg 恒压灌注的对照心脏中，冠状动脉流量随剂量增加而减少，在 400 pmol 时几乎完全消失。在通过将冠状动脉灌注压降至 35 mmHg 使心脏缺血从而使冠状动脉流量减少 76% 的情况下，内皮素 -1 的收缩作用得到了很好的保留。当心脏用含 30 mM KCl 的缓冲液灌注以消除机械活动而不降低细胞外 Ca2+ 浓度时，内皮素 -1 的剂量 - 反应曲线未改变。第四组心脏用无 Ca2+ 的缓冲液灌注，从而消除细胞外 Ca2+ 的来源以及机械活动。在这组中，对内皮素 -1 的收缩反应大部分但并非完全消失，最大收缩作用仅为 19%，而对照心脏中为 87%。我们得出结论，在离体大鼠心脏中，内皮素 -1 在缺血灌注条件下是一种强效的冠状动脉收缩剂，并且机械活动的缺失不影响内皮素 -1 的作用，而细胞外 Ca2+ 的存在对此至关重要。无 Ca2+ 灌注时的小的残余收缩反应可能是由于细胞内储存的 Ca2+ 释放所致。
