Evaluation of beta3-adrenoceptor-mediated relaxation in intact and endotoxin-treated equine digital veins.
Abstract: 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.
Publication Date: 2003-06-28 PubMed ID: 12828256DOI: 10.2460/ajvr.2003.64.708Google Scholar: Lookup
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- Journal Article
Summary
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The research paper presents an investigation into the functional role of beta3-adrenoceptors in the veins found in a horse’s hoof (equine digital veins) and how their functionality is modified when exposed to endotoxins.
Research Methods
- The researchers obtained forelimbs from 30 horses at an abattoir. The veins (equine digital veins) from the lower portions of these forelimbs were carefully collected.
- Segments of these veins were placed in 5-mL organ baths to measure the isometric tension, meaning the tension that develops in the muscle without changing its length.
- Various agonists or activators of beta3-adrenoceptors (beta3-ARs) – SR 58611A, ZD 2079, and ZM 215001 – were introduced to studied their effects on the veins.
Results
- Both in normal condition, and when introduced to these activators, the veins demonstrated concentration-dependent relaxation.
- Relaxation effects caused by Isoprenaline and SR 58611A were either decreased or unaffected by Nadolol, showing that these effects are mediated by beta3-ARs
- Introduction of ZM 215001, used here as a beta3-ARs blocker, resulted in reduced relaxation effects by SR 58611A on the normal veins.
- In the absence of endothelium or when the production of nitric oxide was interrupted, the relaxation effects of Isoprenaline and SR 58611A were significantly reduced.
- Relaxation effects in veins treated with an endotoxin were also significantly reduced.
- Adding cycloheximide (which inhibits protein synthesis) and ibuprofen (which inhibits cyclooxygenase that leads to inflammation) restored the relaxation response to SR 58611A in endotoxin-treated veins.
Conclusions
- Beta3-adrenoceptors are indeed functionally expressed in equine digital veins.
- Exposure to endotoxins, as an in vitro model of laminitis (a disease condition in horses), led to alteration in beta-AR-mediated relaxations in the veins, possibly due to the induction of cyclooxygenase and subsequent prostanoid production.
Cite This Article
APA
Mallem MY, Gogny M, Gautier F, Bucas V, Desfontis JC.
(2003).
Evaluation of beta3-adrenoceptor-mediated relaxation in intact and endotoxin-treated equine digital veins.
Am J Vet Res, 64(6), 708-714.
https://doi.org/10.2460/ajvr.2003.64.708 Publication
Researcher Affiliations
- Unit of Functional Pharmacology (UPSP 5304), National Veterinary School, Atlanpôle, BP 40706, 44307 Nantes, France.
MeSH Terms
- Adrenergic beta-3 Receptor Agonists
- Adrenergic beta-3 Receptor Antagonists
- Animals
- Dose-Response Relationship, Drug
- Endothelium, Vascular / physiology
- Endotoxins / pharmacology
- Horses / physiology
- In Vitro Techniques
- Isoproterenol / pharmacology
- Muscle Relaxation / drug effects
- Muscle, Smooth, Vascular / drug effects
- Nitric Oxide / metabolism
- Nitric Oxide Synthase / antagonists & inhibitors
- Nitric Oxide Synthase / metabolism
- Receptors, Adrenergic, beta-3 / physiology
- Tetrahydronaphthalenes / pharmacology
- Veins / drug effects
Citations
This article has been cited 1 times.- Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J. The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro. Inflamm Res 2014 Aug;63(8):637-47.
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