ANTAGONISM OF EICOSANOID-INDUCED CONTRACTION OF RAT AORTA BY SULFONYLUREAS

Glibenclamide and other sulphonylureas are extensively used as specifi c blockers for ATP-dependent potassium channels in vascular smooth mus cle. 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 sulphonylur eas in rat aorta. The inhibitory effects of sulphonylureas on the cont ractions induced by prostaglandins F-2 alpha, E(2) and D-2, norepineph rine, 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) were exam ined. Glibenclamide significantly inhibited the contractions produced by prostaglandins F-2 alpha E(2) and D-2 but was without effect on res ponses to norepinephrine, 5-HT or KCl. Glimepiride produced significan t attenuation of the responses to all agents tested (5-HT, norepinephr ine, KCl), although the inhibition of the responses to prostaglandin F -2 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 no repinephrine, glibenclamide inhibited the relaxant responses to lemaka lim and pinacidil. Thus, in addition to the effect on ATP-dependent po tassium channels, glibenclamide inhibits responses to prostaglandins F -2 alpha, E(2) and D-2 but not to other agents. This effect is shared by glimepiride, tolbutamide and glipizide.