Effects of H2O2 on membrane potential of smooth muscle cells in rabbit mesenteric resistance artery.
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.
Hattori
Tomonori
T
Department of Cellular and Molecular Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Japan. hattorit@med.nagoya-cu.ac.jp
Kajikuri
Junko
J
Katsuya
Hirotada
H
Itoh
Takeo
T
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
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