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.
Cornelisse
C J
CJ
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48823-1314, USA.
Robinson
N E
NE
Berney
C A
CA
Eberhart
S
S
Hauptman
J E
JE
Derksen
F J
FJ
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