title: Effects of H2O2 on membrane potential of smooth muscle cells in rabbit mesenteric resistance artery.
abstract: The effects of H(2)O(2) on the membrane potential of smooth muscle cells of rabbit mesenteric resistance arteries were investigated. H(2)O(2) (3-30 microM) concentration-dependently hyperpolarized the membrane; this was inhibited by catalase but not by superoxide dismutase or the hydroxyl-radical scavenger dimethylthiourea. The cyclooxygenase inhibitor diclofenac partly inhibited the responses; the subsequent addition of the 5-lipoxygenase inhibitor 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone (AA-861) (but not the cytochrome P(450) inhibitor 17-octadecynoic acid) further attenuated H(2)O(2)-induced hyperpolarizations. The sarcolemmal ATP-sensitive K(+) (K(ATP)) channel inhibitor 1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenylsulfonyl]-3-methylthiourea, sodium salt (HMR-1098), blocked the H(2)O(2)-induced hyperpolarization in the absence and presence of diclofenac. H(2)O(2) increased the production of prostaglandin E(2) and prostacyclin (estimated from its stable metabolite 6-keto-prostaglandin F(1alpha)), both of which produce a HMR-1098-sensitive hyperpolarization in the smooth muscle cells. It is concluded that, in smooth muscle cells of rabbit mesenteric artery, H(2)O(2) increases the synthesis of vasodilator prostaglandins and possibly 5-lipoxygenase products, which produce a hyperpolarization by activating sarcolemmal K(ATP) channels.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Japan. hattorit@med.nagoya-cu.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hattori
authors.forename: Junko
authors.initials: J
authors.lastname: Kajikuri
authors.forename: Hirotada
authors.initials: H
authors.lastname: Katsuya
authors.forename: Takeo
authors.initials: T
authors.lastname: Itoh
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D004008:Diclofenac; D009599:Nitroprusside; D017997:Leukotriene C4; C048081:beraprost; D015121:6-Ketoprostaglandin F1 alpha; D017998:Leukotriene D4; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D015232:Dinoprostone