Increased superoxide anion production by interleukin-1beta impairs nitric oxide-mediated relaxation in resistance arteries.
The present study was designed to analyze the effect of long-term incubation with interleukin-1beta (IL-1beta) on endothelium-dependent relaxation in rat mesenteric resistance arteries. Vessels were incubated in culture medium with or without IL-1beta (10 ng/ml, 14 h). Changes in lumen diameter were recorded in a pressure myograph. Protein expression, nitrite, and superoxide anion (O(2)(.)) production were evaluated by either Western blot or immunofluorescence, Griess reaction, and ethidium fluorescence, respectively. IL-1beta impaired acetylcholine (ACh) and sodium nitroprusside (SNP) vasodilation and increased nitrite and O(2)(.) 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-1beta treatment. Polyethylene glycol superoxide dismutase partially reversed the impairment of ACh relaxation and abolished the O(2)(.) production observed in IL-1beta-treated arteries. The impairment of ACh relaxation induced by IL-1beta 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 microM). However, all these inhibitors improved the impaired SNP response. The results of the present study demonstrate that long-term incubation with IL-1beta induces an impairment of the nitric oxide-mediated relaxation in mesenteric resistance arteries through the production of O(2)(.), mainly from xanthine oxidase.
Jiménez-Altayó
Francesc
F
Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Briones
Ana M
AM
Giraldo
Jesús
J
Planas
Anna M
AM
Salaices
Mercedes
M
Vila
Elisabet
E
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009213:Myography; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014655:Vascular Resistance / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D007375:Interleukin-1; D009573:Nitrites; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase