Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid

C. Zhang, R. Pate, J. P. Eiserich, F. Zhou, S. Kelpke, W. Ma, D. A. Parks, V. Darley-Usmar, C. R. White

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 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 (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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number4 50-4
StatePublished - 2001
Externally publishedYes

Fingerprint

Hypochlorous Acid
Oxidants
Arginine
Acetylcholine
Nitric Oxide
Calcimycin
Endothelium
Calcium Ionophores
Nitric Oxide Synthase Type III
Nitroprusside
Nitrites
Nitrates
Peroxidase
Biological Availability
Sprague Dawley Rats
Endothelial Cells
Wounds and Injuries

Keywords

  • Endothelium
  • Nitric oxide
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Zhang, C., Pate, R., Eiserich, J. P., Zhou, F., Kelpke, S., Ma, W., ... White, C. R. (2001). Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid. American Journal of Physiology - Heart and Circulatory Physiology, 281(4 50-4).

Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid. / Zhang, C.; Pate, R.; Eiserich, J. P.; Zhou, F.; Kelpke, S.; Ma, W.; Parks, D. A.; Darley-Usmar, V.; White, C. R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 281, No. 4 50-4, 2001.

Research output: Contribution to journalArticle

Zhang, C, Pate, R, Eiserich, JP, Zhou, F, Kelpke, S, Ma, W, Parks, DA, Darley-Usmar, V & White, CR 2001, 'Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid', American Journal of Physiology - Heart and Circulatory Physiology, vol. 281, no. 4 50-4.
Zhang, C. ; Pate, R. ; Eiserich, J. P. ; Zhou, F. ; Kelpke, S. ; Ma, W. ; Parks, D. A. ; Darley-Usmar, V. ; White, C. R. / Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid. In: American Journal of Physiology - Heart and Circulatory Physiology. 2001 ; Vol. 281, No. 4 50-4.
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