Antagonism of eicosanoid-induced contraction of rat aorta by sulphonylureas.
Antagonism of eicosanoid-induced contraction of rat aorta by sulphonylureas.
复制标题
磺脲类药物对类花生酸诱导的大鼠主动脉收缩的拮抗作用。
作者：
Zhang,H;Cook,D
格列本脲和其他磺脲类药物广泛用作血管平滑肌ATP依赖性钾通道的特异性阻断剂。然而，格列本脲最近被证明可以抑制血管平滑肌中某些前列腺素类的作用。我们扩展了我们以前的研究，通过检查五种不同的磺脲类药物在大鼠主动脉的舒张作用。观察磺脲类药物对肾上腺素F2α、E2、D2、去甲肾上腺素、5-羟色胺（5-HT）和氯化钾（KCl）引起的离体心肌收缩的抑制作用。格列本脲可显著抑制肾上腺素F2α、E2和D2引起的收缩，但对去甲肾上腺素、5-HT和KCl引起的收缩无影响。尽管对前列腺素F2α反应的抑制作用最明显，但格列美脲可显著减弱对所有试验药物（5-HT、去甲肾上腺素、KCl）的反应。格列吡嗪和甲苯磺丁脲的活性与格列本脲相似，而氯磺丙脲在大鼠主动脉中没有任何拮抗作用。在去甲肾上腺素预收缩的大鼠主动脉中，格列本脲抑制对lemakalim和pinacidil的舒张反应。因此，除了对ATP依赖性钾通道的作用外，格列本脲还抑制对胰高血糖素F2α、E2和D2的反应，但不抑制对其他药物的反应。格列美脲、甲苯磺丁脲和格列吡嗪也具有这种作用。
Glibenclamide and other sulphonylureas are extensively used as specific blockers for ATP-dependent potassium channels in vascular smooth muscle. However, glibenclamide has recently been shown to inhibit actions of some prostanoids in vascular smooth muscle. We extend our previous study by examining the relaxant actions of five different sulphonylureas in rat aorta. The inhibitory effects of sulphonylureas on the contractions induced by prostaglandins F2α, E2 and D2, norepinephrine, 5-hydroxy-tryptamine (5-HT) or potassium chloride (KC1) were examined. Glibenclamide significantly inhibited the contractions produced by prostaglandins F2α, E2and D2but was without effect on responses to norepinephrine, 5-HT or KC1. Glimepiride produced significant attenuation of the responses to all agents tested (5-HT, norepinephrine, KC1), although the inhibition of the responses to prostaglandin F2αwas most pronounced. Glipizide and tolbutamide had activities similar to that of glibenclamide, while chlorpropamide was devoid of any antagonist action in rat aorta. In rat aorta precontracted with norepinephrine, glibenclamide inhibited the relaxant responses to lemakalim and pinacidil. Thus, in addition to the effect on ATP-dependent potassium channels, glibenclamide inhibits responses to prostaglandins F2α, E2and D2but not to other agents. This effect is shared by glimepiride, tolbutamide and glipizide.