Thermographic study of in vivo modulation of vascular responses to phenylephrine and endothelin-1 by dexamethasone in the horse.
BACKGROUND
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.
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48823-1314, USA.
C J
CJ
Cornelisse
N E
NE
Robinson
C A
CA
Berney
S
S
Eberhart
J E
JE
Hauptman
F J
FJ
Derksen
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects*; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006736:Horses / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D013817:Thermography / Q000379:methods / Q000662:veterinary*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D003907:Dexamethasone