内皮素拮抗剂对前列腺素内皮源性收缩因子反应的影响。

Effect of endothelin antagonists on the responses to prostanoid endothelium-derived contracting factor.

Moreau P, Takase H, Lüscher T F

University Hospital, Bern, Switzerland.

Br J Pharmacol. 1996 Jul;118(6):1429-32. doi: 10.1111/j.1476-5381.1996.tb15556.x.

Abstract

The effect of endothelin antagonists on endothelium-dependent contractions was studied in conditions of stimulated endothelium-derived contracting factor (EDCF) release and with exogenous activation of thromboxane A2-endoperoxide receptors in the rat aorta. 2. The incubation of aortic rings with N omega-nitro-L-arginine methyl ester (L-NAME) led to EDCF-mediated contraction upon stimulation with acetylcholine (24 +/- 3% of KCl contraction). When vessels were preincubated with bosentan, an endothelinA- and endothelinB-receptor antagonist, in addition to L-NAME, acetylcholine-induced contraction was reduced to 8 +/- 2% (P < 0.01) of KCl contractions. PD147953, a selective endothelinA-receptor antagonist, reduced the contraction to 14 +/- 4% (P < 0.05) of KCl contractions. 3. Bosentan preincubation produced a significant parallel rightward shift of the contractions to U46619, a selective thromboxane A2 receptor agonist. In contrast, PD147953 failed to exhibit any inhibitory effect on U46619 contractions. 4. These results suggest that endothelin antagonists inhibit EDCF-mediated contractions by blocking endothelinA receptors and that, in addition, bosentan antagonizes the direct stimulation of thromboxane A2 receptors.

摘要

在大鼠主动脉中，研究了内皮素拮抗剂对内皮依赖性收缩的影响，实验条件为刺激内皮衍生收缩因子（EDCF）释放以及外源性激活血栓素A2-内过氧化物受体。2. 用Nω-硝基-L-精氨酸甲酯（L-NAME）孵育主动脉环，会导致乙酰胆碱刺激后EDCF介导的收缩（为氯化钾收缩的24±3%）。当血管先用波生坦（一种内皮素A和内皮素B受体拮抗剂）预孵育，再加入L-NAME时，乙酰胆碱诱导的收缩降至氯化钾收缩的8±2%（P<0.01）。选择性内皮素A受体拮抗剂PD147953可使收缩降至氯化钾收缩的14±4%（P<0.05）。3. 波生坦预孵育使对选择性血栓素A2受体激动剂U46619的收缩产生显著的平行右移。相比之下，PD147953对U46619收缩无抑制作用。4. 这些结果表明，内皮素拮抗剂通过阻断内皮素A受体抑制EDCF介导的收缩，此外，波生坦还拮抗血栓素A2受体的直接刺激。