Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid.

Academic Article


  • 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.
  • Keywords

  • Acetylcholine, Animals, Aorta, Arginine, Biological Availability, Calcimycin, Cattle, Cells, Cultured, Endothelium, Vascular, Hypochlorous Acid, In Vitro Techniques, Inflammation Mediators, Ionophores, Male, Nitrates, Nitric Oxide, Nitrites, Nitroprusside, Oxidants, Rats, Rats, Sprague-Dawley, Vasoconstriction, Vasoconstrictor Agents, Vasodilator Agents
  • Digital Object Identifier (doi)

    Author List

  • Zhang C; Patel R; Eiserich JP; Zhou F; Kelpke S; Ma W; Parks DA; Darley-Usmar V; White CR
  • Start Page

  • H1469
  • End Page

  • H1475
  • Volume

  • 281
  • Issue

  • 4