We examined the relative contribution of endothelial and vascular smooth muscle-derived prostaglandins and endothelium-derived relaxing factor in modulating both the large coronary artery and resistance vessel responses to thromboxane in vivo. Vascular responses to the thromboxane analogue U46619 were measured in four separate experimental protocols: 1) The vascular responses were measured in the presence and absence of intact endothelium to examine the role of endothelium-derived vasodilators. 2) Responses were measured in the presence of intact endothelium before and after inhibition of cyclooxygenase with indomethacin to examine the role of endothelial and vascular smooth muscle-derived prostaglandins. 3) Responses were measured after endothelial removal before and after indomethacin to examine the role of vascular smooth muscle-derived prostaglandins. 4) Responses were measured after indomethacin and before and after removal of endothelium to examine the role of endothelium-derived relaxing factor. In anesthetized dogs (n = 41) that underwent constant pressure perfusion of the left anterior descending coronary artery (LAD), LAD diameter was measured with sonomicrometer crystals, and coronary flow was measured with an electromagnetic flow probe. Intracoronary infusion of U46619 (0.01-1.0 microgram/min) produced a dose-dependent constriction of LAD. Constriction of the LAD was augmented after endothelial removal, after indomethacin treatment in both the presence and absence of endothelium, and after removal of the endothelium in the presence of indomethacin. Inhibition of prostaglandin synthesis had the greatest effect of augmenting constriction of LAD to thromboxane. Coronary flow was decreased by U46619 only in the presence of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

译文

我们检查了内皮和血管平滑肌衍生的前列腺素和内皮衍生的舒张因子在体内调节大冠状动脉和阻力血管对血栓烷的反应中的相对贡献。在四个独立的实验方案中测量了对血栓素类似物U46619的血管反应: 1) 在存在和不存在完整内皮的情况下测量血管反应,以检查内皮衍生的血管扩张剂的作用。2) 在吲哚美辛抑制环氧合酶之前和之后,在完整的内皮存在下测量反应,以检查内皮和血管平滑肌衍生的前列腺素的作用。3) 在吲哚美辛前后测量内皮去除后的反应,以检查血管平滑肌衍生的前列腺素的作用。4) 在吲哚美辛之后以及去除内皮之前和之后测量反应,以检查内皮衍生的松弛因子的作用。在接受左前降支冠状动脉 (LAD) 恒压灌注的麻醉犬 (n = 41) 中,用sonomicrometer晶体测量LAD直径,并用电磁流量探针测量冠状动脉流量。冠状动脉内输注U46619 (0.01-1.0微克/分钟) 产生LAD的剂量依赖性收缩。内皮去除后,在存在和不存在内皮的情况下进行吲哚美辛处理后,以及在存在吲哚美辛的情况下去除内皮后,LAD的收缩增加。抑制前列腺素的合成具有最大的作用,可以增加LAD对血栓烷的收缩。只有在吲哚美辛存在的情况下,U46619才能减少冠状动脉血流。(摘要截短于250字)

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