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

The present study was designed to analyze the effect of long-term incubation with interleukin-1 beta (IL-1 beta) on endothelium-dependent relaxation in rat mesenteric resistance arteries. Vessels were incubated in culture medium with or without IL-1 beta(10 ng/ml, 14 h). Changes in lumen diameter were recorded in a pressure myograph. Protein expression, nitrite, and superoxide anion (O-2 radical anion.) production were evaluated by either Western blot or immunofluorescence, Griess reaction, and ethidium fluorescence, respectively. IL-1 beta impaired acetylcholine (ACh) and sodium nitroprusside (SNP) vasodilation and increased nitrite and O-2 radical adion. production and inducible nitric-oxide synthase (iNOS), xanthine oxidase, and p22(phox) expression. However, neither endothelial nitric-oxide synthase (NOS) nor soluble guanylate cyclase protein expression were affected by IL-1 beta treatment. Polyethylene glycol superoxide dismutase partially reversed the impairment of ACh relaxation and abolished the O-2 radical anion production observed in IL-1 beta-treated arteries. The impairment of ACh relaxation induced by IL-1 beta 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 mu M). However, all these inhibitors improved the impaired SNP response. The results of the present study demonstrate that long-term incubation with IL-1 beta induces an impairment of the nitric oxide-mediated relaxation in mesenteric resistance arteries through the production of O-2 radical adion, mainly from xanthine oxidase.