title: Comparison of the pharmacological properties of EDHF-mediated vasorelaxation in guinea-pig cerebral and mesenteric resistance vessels.
abstract: In the presence of L-NNA (100 microM), indomethacin (10 microM) and ODQ (10 microM), acetylcholine induced a concentration-dependent vasorelaxation of guinea-pig mesenteric and middle cerebral arteries precontracted with cirazoline or histamine, but not with high K(+), indicating the contribution of an endothelium-derived hyperpolarizing factor (EDHF). In cerebral arteries, charybdotoxin (ChTX; 0.1 microM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 microM), 4-aminopyridine (4-AP, 1 mM), or barium (30 microM) significantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 microM) had no affect in either the mesenteric or cerebral artery. Neither clotrimazole (1 microM) nor 7-ethoxyresorufin (3 microM) affected EDHF-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 microM), a selective anandamide transport inhibitor, did not affect the vasorelaxation response to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and apamin-sensitive, but SR 141816A-insensitive manner. Ouabain (100 microM) almost abolished EDHF-mediated relaxation in the mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the addition of K(+) (5 - 20 mM) to precontracted guinea-pig cerebral or mesenteric artery induced further vasoconstriction. These data suggest that in the guinea-pig mesenteric and cerebral arteries different EDHFs mediate acetylcholine-induced relaxation, however, EDHF is unlikely to be mediated by K(+).
authors.affiliation: Smooth Muscle Research Group and Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1 Canada.
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: W C
authors.initials: WC
authors.lastname: Cole
authors.forename: C R
authors.initials: CR
authors.lastname: Triggle
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D001095:Arachidonic Acids; D001685:Biological Factors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011810:Quinoxalines; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D019335:Nitroarginine; D009569:Nitric Oxide; D010042:Ouabain; D003577:Cytochrome P-450 Enzyme System; D015761:4-Aminopyridine; D000109:Acetylcholine; C014282:cirazoline; D005905:Glyburide; C107594:N-(4-hydroxyphenyl)arachidonylamide; D007213:Indomethacin