Evaluation of beta3-adrenoceptor-mediated relaxation in intact and endotoxin-treated equine digital veins.
OBJECTIVE
To investigate the functional expression of beta3-adrenoceptors (beta3-ARs) in equine digital veins (EDVs) and to examine whether beta3-AR relaxation was altered in EDVs incubated with endotoxin.


METHODS
Forelimbs obtained from 30 horses.


METHODS
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 beta3-AR agonists (SR 58611A, ZD 2079, and ZM 215001).


RESULTS
In intact EDVs, isoprenaline, SR 58611A, ZD 2079, and ZM 215001 induced concentration-dependent relaxation. Isoprenaline and SR 58611A-induced relaxations were reduced or unaffected by nadolol, respectively. In intact EDVs, SR 58611A-induced relaxation was significantly reduced in the presence of 2 microM ZM 215001 (used as a beta3-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
Beta3-adrenoceptors are functionally expressed in EDVs. Incubation in the presence of endotoxin, used as an in vitro model of laminitis, induced an alteration of beta-AR-mediated relaxations in EDVs, which could be the consequence of cyclooxygenase induction and subsequent prostanoid production.
Mallem
Mohamed Y
MY
Unit of Functional Pharmacology (UPSP 5304), National Veterinary School, Atlanpôle, BP 40706, 44307 Nantes, France.
Gogny
Marc
M
Gautier
Freddy
F
Bucas
Veronique
V
Desfontis
Jean-Claude
JC
D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D006736:Horses / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014680:Veins / Q000187:drug effects*
D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D004731:Endotoxins; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; C076252:amibegron