Thermographic study of in vivo modulation of vascular responses to phenylephrine and endothelin-1 by dexamethasone in the horse.
Abstract: In vitro, glucocorticoids potentiate vasoconstriction of equine digital vessels to catecholamines and this has been implicated as a mechanism of glucocorticoid-induced laminitis. This observation has never been confirmed in vivo. Objective: To study the effects of glucocorticoid therapy on vasoconstrictor responsiveness in the horse in vivo. Methods: In a blinded, randomised cross-over experiment, 9 horses were treated with either dexamethasone (0.1 mg/kg bwt i.v. q. 24 h) or saline i.v. for 6 days. The changes in local average skin temperature before (baseline) and after intradermal injections of the alpha1-adrenoceptor agonist phenylephrine (PHE; 10(-4), 10(-5), 10(-6), 10(-7) and 10(-8) mol/l), endothelin-1 (ET-1; 10(-5), 10(-6), 10(-7), 10(-8) and 10(-9) mol/l) or ET-1 plus a blocker (BQ-123 10(-6) mol/l; RES-701 10(-6) mol/l; and L-NAME 10(-4) mol/l) were investigated with a thermograph. Results: Dexamethasone (DEX) decreased baseline skin temperatures, suggesting reduced blood flow as a consequence of an increase in vasomotor tone. This was accompanied by potentiation of the response to PHE as demonstrated by a left shift in the dose-response curve and a decrease in the EC50. Dexamethasone did not potentiate ET-1, but the interplay with the lower baseline temperature resulted in a significantly lower skin temperature for this vasoconstrictor after DEX. The different ET-1 blockers had no effect on ET-1 modulated skin temperatures. Conclusions: Dexamethasone decreases skin perfusion. This is accompanied by a potentiated alpha1-adrenoceptor agonist response and a greater response to ET-1. Conclusions: Glucocorticoid therapy probably decreases perfusion of the equine hoof. During disease states that already are characterised by hypoperfusion and/or increased levels of circulating catecholamines, glucocorticoid therapy could, according to the vascular model of laminitis, tilt the balance in favour of laminitis.
Publication Date: 2006-03-16 PubMed ID: 16536380DOI: 10.2746/042516406776563251Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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The research investigates how a drug commonly administered in horses called dexamethasone (a glucocorticoid) affects blood flow and how these changes could potentially lead to laminitis, a painful inflammatory condition of the hoof.
Objective and Methodology
- The researchers aimed to study effects of glucocorticoid therapy, using dexamethasone, on the responsiveness of blood vessels to constriction in horses, in real-life conditions.
- In this blind, randomized cross-over experiment, 9 horses were either treated with dexamethasone or saline for six days.
- Changes in local average skin temperature were studied before and after injections of two substances – phenylephrine, which is an adrenoceptor agonist exerting constricting effects, and endothelin-1, a potent vasoconstrictor. Different dosages of each substance were tested.
- The researchers also looked at what happened when the endothelin-1 was coupled with a blocker.
- The skin temperature measured via a thermograph served as a proxy to assess the modulation of blood flow. Lower temperatures suggested reduced blood flow, indicating increased constriction of the blood vessels.
Results
- It was found out that dexamethasone decreased skin temperatures–which implies decreased blood flow due to enhanced vasoconstriction.
- Moreover, this glucocorticoid seemed to amplify the response to phenylephrine, which was evidenced by a change in the dose-response curve and a decrease in the effective concentration for 50% response (EC50).
- When it came to endothelin-1, dexamethasone didn’t amplify its effects. However, given the lower initial temperature under dexamethasone, the effect of endothelin-1 was more pronounced.
- Interestingly, none of the endothelin-1 blockers seemed to affect the temperature changes they observed.
Conclusions
- Overall, the research concluded that dexamethasone reduces blood flow, amplifies the response to phenylephrine, and indirectly leads to a notable vasoconstricting effect of endothelin-1.
- The authors suggest that these outcomes of glucocorticoid therapy could potentially aggravate the risks of developing laminitis, especially in conditions already characterized by limited blood flow or heightened catecholamine levels.
Cite This Article
APA
Cornelisse CJ, Robinson NE, Berney CA, Eberhart S, Hauptman JE, Derksen FJ.
(2006).
Thermographic study of in vivo modulation of vascular responses to phenylephrine and endothelin-1 by dexamethasone in the horse.
Equine Vet J, 38(2), 119-126.
https://doi.org/10.2746/042516406776563251 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48823-1314, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / pharmacology
- Area Under Curve
- Body Temperature / drug effects
- Cross-Over Studies
- Dexamethasone / pharmacology
- Dose-Response Relationship, Drug
- Endothelin-1 / pharmacology
- Female
- Horses / physiology
- Phenylephrine / pharmacology
- Skin / blood supply
- Thermography / methods
- Thermography / veterinary
- Vasoconstrictor Agents / pharmacology
Citations
This article has been cited 2 times.- Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review.. J Vet Intern Med 2021 Jul;35(4):2045-2057.
- Textor JA, Clark KC, Walker NJ, Aristizobal FA, Kol A, LeJeune SS, Bledsoe A, Davidyan A, Gray SN, Bohannon-Worsley LK, Woolard KD, Borjesson DL. Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.. Stem Cells Transl Med 2018 Jan;7(1):98-108.
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