title: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries.
abstract: The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several vasodilating factors, including prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF). We have recently identified that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in mice. The present study was designed to examine whether this is also the case in humans. Bradykinin elicited endothelium-dependent relaxations and hyperpolarizations in the presence of indomethacin and N(omega)-nitro-l-arginine, which thus were attributed to EDHF, in human mesenteric arteries. The EDHF-mediated relaxations were significantly inhibited by catalase, an enzyme that specifically decomposes H(2)O(2), whereas catalase did not affect endothelium-independent hyperpolarizations to levcromakalim. Exogenous H(2)O(2) elicited relaxations and hyperpolarizations in endothelium-stripped arteries. Gap junction inhibitor 18alpha-glycyrrhetinic acid partially inhibited, whereas inhibitors of cytochrome P450 did not affect the EDHF-mediated relaxations. These results indicate that H(2)O(2) is also a primary EDHF in human mesenteric arteries with some contribution of gap junctions.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matoba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubota
authors.forename: Keiko
authors.initials: K
authors.lastname: Morikawa
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiki
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kunihiro
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mukai
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hirakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000368:Aged; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D046508:Culture Techniques; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D013426:Sulfaphenazole / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019806:Cromakalim; D013426:Sulfaphenazole; C119129:18alpha-glycyrrhetinic acid; D006861:Hydrogen Peroxide; D002374:Catalase; D006034:Glycyrrhetinic Acid; D001920:Bradykinin