Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid

• Published in: American journal of physiology. Heart and circulatory physiology 2001-10, Vol.281 (4), p.H1469-H1475
• Main Authors: Zhang, Chunxiang, Patel, Rakesh, Eiserich, Jason P, Zhou, Fen, Kelpke, Stacey, Ma, Wenxin, Parks, Dale A, Darley-Usmar, Victor, White, C. Roger
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Aorta - drug effects; Aorta - enzymology; Arginine - pharmacology; Biological Availability; Calcimycin - pharmacology; Cattle; Cells, Cultured; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Hypochlorous Acid - pharmacology; In Vitro Techniques; Inflammation Mediators - pharmacology; Ionophores - pharmacology; Male; Nitrates - antagonists & inhibitors; Nitric Oxide - metabolism; Nitrites - antagonists & inhibitors; Nitroprusside - pharmacology; Oxidants - pharmacology; Rats; Rats, Sprague-Dawley; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2001.281.4.h1469

1  Departments of Medicine, Vascular Biology and Hypertension Program, 2  Pathology, 3  Anesthesiology, and 4  Center for Free Radical Biology, University of Alabama at Birmingham; Birmingham, Alabama 35294; and 5  Division of Nephrology, Department of Internal Medicine, University of California at Davis, Davis, California 95616 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 µM) 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 (NO ) and nitrite (NO ). 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. nitric oxide; endothelium; smooth muscle