Kähler J, Conforto A, Termin A, Bing R J
Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, CA 91105.
Int J Cardiol. 1993 Mar;38(3):213-23. doi: 10.1016/0167-5273(93)90239-d.
The effects of cell free superfusates from freshly harvested bovine endothelial cells attached to microcarrier beads on the isolated rabbit and rat heart and on superfused rabbit jugular veins were observed. Cell free conditioned filtrates from freshly harvested cells caused marked diminution in coronary flow and cardiac output in the isolated rabbit heart; in the perfused rat heart an increase in coronary perfusion pressure and a decline in left ventricular systolic tension and maximal left ventricular contractility (dP/dt) were recorded. Marked differences were found between changes induced by conditioned filtrate as compared to synthetic endothelin. Endothelin as present in conditioned filtrate could not account for the pronounced effect on coronary perfusion pressure, dp/dt and cardiac output induced by conditioned filtrate; more than one hundred times that of synthetic endothelin was needed to achieve comparable cardiodynamic effects. This suggested that additional non-prostanoid vasoconstrictor substance or substances are produced by freshly harvested endothelial cells. This conclusion was supported by the observation that BQ-123, a specific inhibitor of endothelin A (ETA) receptor significantly prevented contractions by endothelin, while failing to inhibit those induced by freshly harvested endothelial cells. These constrictor substances may be leukotrienes.
观察了附着于微载体珠上的新鲜收获的牛内皮细胞的无细胞超滤液对离体兔和大鼠心脏以及对灌注兔颈静脉的影响。新鲜收获细胞的无细胞条件滤液导致离体兔心脏的冠状动脉血流量和心输出量显著减少;在灌注的大鼠心脏中,记录到冠状动脉灌注压升高,左心室收缩张力和左心室最大收缩力(dP/dt)下降。与合成内皮素相比,条件滤液诱导的变化存在显著差异。条件滤液中存在的内皮素不能解释其对冠状动脉灌注压、dp/dt和心输出量的明显影响;需要比合成内皮素多一百倍以上的量才能产生相当的心脏动力学效应。这表明新鲜收获的内皮细胞会产生额外的非前列腺素类血管收缩物质。这一结论得到了以下观察结果的支持:内皮素A(ETA)受体的特异性抑制剂BQ-123能显著抑制内皮素引起的收缩,而不能抑制新鲜收获的内皮细胞诱导的收缩。这些收缩物质可能是白三烯。