Evaluation of the role of superoxide anions in endotoxin-induced impairment of beta-adrenoceptor-mediated vasodilation in equine digital veins

摘要

Objective-To investigate the role of superoxide anions in the lipopolysaccharide (LPS)-induced impairment of beta-adrenoceptor-mediated equine digital vein (EDV) vasodilation.Sample Population-EDVs isolated from forelimbs of 24 healthy adult horses.Procedures-Endothelium-intact or endothelium-denuded EDV rings were incubated with or without LPS (10 mu g/mL) of Escherichia coil (O55:135) for 4 hours. Cumulative concentration-relaxation curves resulting from administration of isoprenaline, a nonselective beta-adrenoceptor agonist, or from administration of SR 58611A, a selective beta(3)-adrenoceptor agonist, were recorded in phenylephrine-preconstricted EDVs in the absence or the presence of superoxide dismutase (200 U/mL). Isoprenaline-induced relaxation was also evaluated with or without the cyclooxygenase inhibitors indomethacin (10 mu M) and NS-398 (10 mu M).Results-Isoprenaline and SR 58611A induced concentration-dependent relaxation of EDV rings, which was inhibited by LPS exposure. Superoxide dismutase abolished the inhibitory effect of LPS on the isoprenaline- and SR 58611A-mediated relaxation. Pretreatment of the LPS-treated EDVs with indomethacin or NS-398 restored the isoprenaline-mediated relaxation and abolished the LPS-induced impairment to a similar extent as superoxide dismutase.Conclusions and Clinical Relevance-Results supported a role of superoxide anions in the LPS-induced impairment of beta-adrenoceptor-mediated EDV vasodilation. The LPS-induced oxidative stress in EDVs may contribute to vascular dysfunctions associated with laminitis in horses. (Am J Vet Res 2010;71:773-779)