title: Characterization of endothelium-dependent relaxation independent of NO and prostaglandins in guinea pig coronary artery.
abstract: In the presence of N omega-nitro-L-arginine and indomethacin, acetylcholine (ACh) induced endothelium-dependent relaxation in guinea pig coronary artery preconstricted with 9,11-dideoxy-9 alpha, 11 alpha-epoxymethano prostaglandin F2 alpha. 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 N omega-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.
authors.affiliation: Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yamanaka
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Goto
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D015221:Potassium Channels / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D014664:Vasodilation
chemical_list: D001685:Biological Factors; D005231:Fatty Acids, Unsaturated; D015221:Potassium Channels; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; C047008:17-octadecynoic acid; D010741:Phospholipases A; D054467:Phospholipases A2; D000109:Acetylcholine; D002118:Calcium; D007213:Indomethacin