Objective: To investigate the role of superoxide anions in the lipopolysaccharide (LPS)-induced impairment of β-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 μg/mL) of Escherichia coli (O55:B5) for 4 hours. Cumulative concentration-relaxation curves resulting from administration of isoprenaline, a nonselective β-adrenoceptor agonist, or from administration of SR 58611A, a selective β₃-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 (10μM) and NS-398 (10μM).

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 β-adrenoceptor-mediated EDV vasodilation. The LPS-induced oxidative stress in EDVs may contribute to vascular dysfunctions associated with laminitis in horses.