Endothelial dysfunction is induced by proinflammatory oxidant hypochlorousacid

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study test s the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in t he vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1-50 muM) 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 e ffect of HOCl on ACh-induced relaxation was reversed by exposure of ring se gments 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 redu ction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition Of L-arginine. These data suggest that HOCl i nduces endothelial dysfunction via modification of L-arginine.