Increased superoxide anion production by interleukin-1β impairs nitric oxide-mediated relaxation in resistance arteries

Francesc Jiménez-Altayó, Ana M. Briones, Jesús Giraldo, Anna M. Planas, Mercedes Salaices, Elisabet Vila

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59 Citations (Scopus)


The present study was designed to analyze the effect of long-term incubation with interleukin-1β (IL-1β) on endothelium-dependent relaxation in rat mesenteric resistance arteries. Vessels were incubated in culture medium with or without IL-1β (10 ng/ml, 14 h). Changes in lumen diameter were recorded in a pressure myograph. Protein expression, nitrite, and superoxide anion (O2.-) production were evaluated by either Western blot or immunofluorescence, Griess reaction, and ethidium fluorescence, respectively. IL-1β impaired acetylcholine (ACh) and sodium nitroprusside (SNP) vasodilation and increased nitrite and O2.- production and inducible nitric-oxide synthase (iNOS), xanthine oxidase, and p22phox expression. However, neither endothelial nitric-oxide synthase (NOS) nor soluble guanylate cyclase protein expression were affected by IL-1β treatment. Polyethylene glycol superoxide dismutase partially reversed the impairment of ACh relaxation and abolished the O 2.- production observed in IL-1β-treated arteries. The impairment of ACh relaxation induced by IL-1β was also partially reversed by the xanthine oxidase inhibitor allopurinol (1 mM) but not by either the NADPH oxidase inhibitor apocynin (0.3 mM) or the inducible NOS inhibitor N-3-aminomethylbenzylacetamidine (1 μM). However, all these inhibitors improved the impaired SNP response. The results of the present study demonstrate that long-term incubation with IL-1β induces an impairment of the nitric oxide-mediated relaxation in mesenteric resistance arteries through the production of O2.-, mainly from xanthine oxidase. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.
Original languageEnglish
Pages (from-to)42-52
JournalJournal of Pharmacology and Experimental Therapeutics
Publication statusPublished - 1 Jan 2006


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