title: Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid.
abstract: The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1-50 microM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187. HOCl treatment significantly impaired both ACh- and A23187-mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to L-arginine but not D-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO3(-) and nitrite (NO2(-). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of L-arginine. These data suggest that HOCl induces endothelial dysfunction via modification of L-arginine.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.forename: J P
authors.initials: JP
authors.lastname: Eiserich
authors.forename: F
authors.initials: F
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Kelpke
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.forename: D A
authors.initials: DA
authors.lastname: Parks
authors.forename: V
authors.initials: V
authors.lastname: Darley-Usmar
authors.forename: C R
authors.initials: CR
authors.lastname: White
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001120:Arginine / Q000494:pharmacology; D001682:Biological Availability; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009566:Nitrates / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D007476:Ionophores; D009566:Nitrates; D009573:Nitrites; D016877:Oxidants; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000001:Calcimycin; D006997:Hypochlorous Acid; D001120:Arginine; D000109:Acetylcholine