Objective—To investigate the functional expression
of β3-adrenoceptors (β3-ARs) in equine digital veins
(EDVs) and to examine whether β3-AR relaxation was
altered in EDVs incubated with endotoxin.
Sample Population—Forelimbs obtained from 30
Procedure—Forelimbs were obtained from horses in
an abattoir. Equine digital veins were carefully
removed from distal portions of the forelimbs. Rings
of dissected EDVs were mounted in 5-mL organ
baths to record isometric tension in the presence of
various β3-AR agonists (SR 58611A, ZD 2079, and ZM
Results—In intact EDVs, isoprenaline, SR 58611A,
ZD 2079, and ZM 215001 induced concentrationdependent
relaxation. Isoprenaline and SR 58611Ainduced
relaxations were reduced or unaffected by
nadolol, respectively. In intact EDVs, SR 58611Ainduced
relaxation was significantly reduced in the
presence of 2µM ZM 215001 (used as a β3-AR antagonist).
In endothelium-denuded EDVs or intact EDVs
in the presence of a nitric oxide synthase inhibitor,
isoprenaline and SR 58611A-induced relaxations were
significantly decreased. The endothelium-independent
relaxation to SR 58611A was significantly inhibited
in the presence of ZM 215001. In endotoxin-treated
EDV, isoprenaline- and SR 58611A-induced relaxations
were significantly reduced. In these conditions,
cycloheximide (a protein synthesis inhibitor) and
ibuprofen (a cyclooxygenase inhibitor) restored the
relaxant response to SR 58611A.
Conclusions and Clinical Relevance—β3-Adrenoceptors
are functionally expressed in EDVs.
Incubation in the presence of endotoxin, used as an in
vitro model of laminitis, induced an alteration of β-ARmediated
relaxations in EDVs, which could be the
consequence of cyclooxygenase induction and subsequent
prostanoid production. (Am J Vet Res 2003;64:708–714)
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.