Antagonism of eicosanoid-induced contraction of rat aorta by sulphonylureas.
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 F2 alpha, E2 and D2, norepinephrine, 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) were examined. Glibenclamide significantly inhibited the contractions produced by prostaglandins F2 alpha, E2 and D2 but was without effect on responses to norepinephrine, 5-HT or KCl. Glimepiride produced significant attenuation of the responses to all agents tested (5-HT, norepinephrine, KCl), although the inhibition of the responses to prostaglandin F2 alpha was 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 F2 alpha, E2 and D2 but not to other agents. This effect is shared by glimepiride, tolbutamide and glipizide.
Department of Surgery, University of Alberta, Edmonton, Canada.
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D000818:Animals; D001011:Aorta; D015777:Eicosanoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D015777:Eicosanoids; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D012701:Serotonin; D009638:Norepinephrine