Neubauer S, Zimmermann S, Hirsch A, Pulzer F, Tian R, Bauer W, Bauer B, Ertl G
Medizinische Universitätsklinik, Würzburg, Germany.
J Mol Cell Cardiol. 1991 Dec;23(12):1397-409. doi: 10.1016/0022-2828(91)90186-p.
The effects of the vasoconstrictor peptide endothelin-1 were examined in the isolated heart during hypoxia, reoxygenation and reperfusion. 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 to 400 pmol in five groups of hearts. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol in control hearts. In hearts subjected to mild hypoxia (perfusate PO2 approximately 150 mmHg), the constrictor effect of endothelin-1 was attenuated at moderate dose compared to control hearts (4 vs. 16% flow reduction at 40 pmol; P less than 0.05). The constrictor effect was unaltered in hearts subjected to either 60 min of severe hypoxia (PO2 approximately 35 mmHg) followed by reoxygenation or to 10 min of total ischemia followed by reperfusion (stunning). When hearts were reperfused following 30 min of total ischemia (irreversible injury), the constrictor response to endothelin-1 was potentiated compared to control (e.g. 36 vs. 16% flow reduction at 40 pmol; P less than 0.05). We conclude that endothelin-1 is a potent coronary constrictor in hypoxic, reoxygenated and reperfused heart. The constrictor effect is attenuated during hypoxia, most likely due to the presence of counteracting vasodilator metabolites. During reperfusion, the constrictor effect is unchanged in stunned myocardium, but is augmented in irreversibly injured heart, due to either increased endothelin-1 binding sites or loss of counteracting vasodilator mechanisms such as prostaglandins and/or endothelium-derived relaxing factor.
在离体心脏的缺氧、复氧和再灌注过程中，研究了血管收缩肽内皮素 -1 的作用。以恒压用 Krebs - Henseleit 缓冲液灌注等容的大鼠心脏。在五组心脏中，获得了 0.04 至 400 pmol 内皮素 -1 推注的累积剂量 - 反应曲线。在对照心脏中，冠状动脉流量随剂量增加而下降，在 400 pmol 时几乎完全消失。在轻度缺氧（灌注液 PO2 约为 150 mmHg）的心脏中，与对照心脏相比，内皮素 -1 的收缩作用在中等剂量时减弱（40 pmol 时流量减少 4% 对 16%；P 小于 0.05）。在经历 60 分钟严重缺氧（PO2 约为 35 mmHg）后复氧或经历 10 分钟全心缺血后再灌注（心肌顿抑）的心脏中，收缩作用未改变。当心脏在 30 分钟全心缺血（不可逆损伤）后再灌注时，与对照相比，对内皮素 -1 的收缩反应增强（例如，40 pmol 时流量减少 36% 对 16%；P 小于 0.05）。我们得出结论，内皮素 -1 是缺氧、复氧和再灌注心脏中的一种强效冠状动脉收缩剂。在缺氧期间，收缩作用减弱，最可能是由于存在起抵消作用的血管舒张代谢产物。在再灌注期间，在顿抑心肌中收缩作用不变，但在不可逆损伤的心脏中增强，这是由于内皮素 -1 结合位点增加或诸如前列腺素和 / 或内皮衍生舒张因子等起抵消作用的血管舒张机制丧失所致。
