TY - JOUR T1 - Characterization of Endothelium-Dependent Relaxation Independent of NO and Prostaglandins in Guinea Pig Coronary Artery JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 480 LP - 489 VL - 285 IS - 2 AU - Akihiro Yamanaka AU - Tomohisa Ishikawa AU - Katsutoshi Goto Y1 - 1998/05/01 UR - http://jpet.aspetjournals.org/content/285/2/480.abstract N2 - In the presence of Nω-nitro-l-arginine and indomethacin, acetylcholine (ACh) induced endothelium-dependent relaxation in guinea pig coronary artery preconstricted with 9,11-dideoxy-9α,11α-epoxymethano prostaglandin F2α. Dexamethasone and arachidonyltrifluoromethyl ketone, inhibitors of phospholipase A2, and 17-octadecynoic acid, an inhibitor of cytochrome P450 epoxygenase, had no effect on the response to ACh. Although proadifen, which is used widely as an inhibitor of cytochrome P450-dependent enzymes, suppressed the ACh-induced relaxation, the drug also inhibited the relaxation induced by cromakalim, a K+channel opener. In isolated smooth muscle cells of guinea pig coronary artery, proadifen, but not 17-octadecynoic acid, almost abolished delayed rectifier K+ current. Epoxyeicosatrienoic acids failed to relax the artery. Apamin and iberiotoxin, inhibitors of small- and large-conductance Ca++-activated K+channels, respectively, did not affect the relaxation induced by ACh. A combination of charybdotoxin plus apamin, but not iberiotoxin plus apamin, abolished the response. However, the combination of charybdotoxin plus apamin had no effect on ACh-induced increase in intracellular free Ca++ concentration in endothelial cells. These results suggest that epoxyeicosatrienoic acids do not contribute to Nω-nitro-l-arginine/indomethacin-resistant relaxation induced by ACh in the guinea pig coronary artery. The present study also proposes that K+ channels on vascular smooth muscle cells, which both charybdotoxin and apamin must affect for inhibition to occur, are the target for endothelium-derived hyperpolarizing factor. The American Society for Pharmacology and Experimental Therapeutics ER -