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

Mohamed Y. MallemFrom ONIRIS, Unit of Animal Pathophysiology and Functional Pharmacology (UPSP 5304), Atlanpole-La C.hantrerie, BP 40706, Nantes, F-44307, France and Université Nantes Angers Le Mans, Nantes, France.

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Aurélie ThuleauFrom ONIRIS, Unit of Animal Pathophysiology and Functional Pharmacology (UPSP 5304), Atlanpole-La C.hantrerie, BP 40706, Nantes, F-44307, France and Université Nantes Angers Le Mans, Nantes, France.

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Jacques NoireaudFrom ONIRIS, Unit of Animal Pathophysiology and Functional Pharmacology (UPSP 5304), Atlanpole-La C.hantrerie, BP 40706, Nantes, F-44307, France and Université Nantes Angers Le Mans, Nantes, France.

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Jean-Claude DesfontisFrom ONIRIS, Unit of Animal Pathophysiology and Functional Pharmacology (UPSP 5304), Atlanpole-La C.hantrerie, BP 40706, Nantes, F-44307, France and Université Nantes Angers Le Mans, Nantes, France.

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Marc GognyFrom ONIRIS, Unit of Animal Pathophysiology and Functional Pharmacology (UPSP 5304), Atlanpole-La C.hantrerie, BP 40706, Nantes, F-44307, France and Université Nantes Angers Le Mans, Nantes, France.

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Abstract

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.

Abstract

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.

Contributor Notes

Address correspondence to Dr. Mallem (yassine.mallem@oniris-nantes.fr).