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Characterization and comparison of the responses of equine digital arteries and veins to endothelin-1

Lisa M. Katz DVM, MS1,2, Celia M. Marr BVMS, MVM, PhD3, and Jonathan Elliott MA, VetMB, PhD4
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  • 1 Department of Veterinary Clinical Sciences, University of London, The Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
  • | 2 Present address is Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
  • | 3 Department of Veterinary Clinical Sciences, University of London, The Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
  • | 4 Department of Veterinary Basic Science, University of London, The Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, United Kingdom.

Abstract

Objective—To compare the responses of equine digital arteries (EDAs) and equine digital veins (EDVs) to endothelin-1 (ET-1) and determine the role of the endothelium and type of receptors involved in the modulation and mediation of those responses, respectively.

Sample Population—5 to 9 palmar digital vessels/experiment from 28 healthy horses.

Procedure—Rings of dissected vessels were mounted under tension between force transducer wires in organ baths containing Krebs-Henseleit solution at 30oC. Responses of EDAs and EDVs (with intact [+e] or denuded [–e] endothelium) to cumulative concentrations of ET-1 (10–10 to 3 × 10–7 M) were compared. For (+e)EDAs and (+e)EDVs precontracted with a thromboxane-mimetic (U44069; 10–8 M) and (–e)EDAs and (–e)EDVs, responses to an ETB receptor agonist (S6c; 10–10 to 3 × 10–7 M) were evaluated. Responses to ET-1 (10–7 M) in (–e)EDAs and (–e)EDVs were evaluated after incubation with an ETA receptor antagonist (BQ- 123; 3 × 10–7 M), an ETB receptor antagonist (BQ-788; 3 × 10–7 M), or vehicle solution.

Results—Endothelin-1 induced a concentrationdependent contraction of endothelium-intact and -denuded EDAs and EDVs; EDVs were more sensitive. Neither vessel type relaxed in response to S6c, although 2 of the (–e)EDAs contracted mildly. Whereas BQ-123 inhibited the (–e)EDA and (–e)EDV responses to ET-1, BQ-788 had no effect.

Conclusions and Clinical Relevance—Endothelin-1 induced digital vasoconstriction (marked constriction in veins). This action was unaffected by endothelium and mediated predominantly by ETA receptors. These findings suggest ET-1 can induce selective digital venoconstriction. (Am J Vet Res 2003;64:1438–1443

Abstract

Objective—To compare the responses of equine digital arteries (EDAs) and equine digital veins (EDVs) to endothelin-1 (ET-1) and determine the role of the endothelium and type of receptors involved in the modulation and mediation of those responses, respectively.

Sample Population—5 to 9 palmar digital vessels/experiment from 28 healthy horses.

Procedure—Rings of dissected vessels were mounted under tension between force transducer wires in organ baths containing Krebs-Henseleit solution at 30oC. Responses of EDAs and EDVs (with intact [+e] or denuded [–e] endothelium) to cumulative concentrations of ET-1 (10–10 to 3 × 10–7 M) were compared. For (+e)EDAs and (+e)EDVs precontracted with a thromboxane-mimetic (U44069; 10–8 M) and (–e)EDAs and (–e)EDVs, responses to an ETB receptor agonist (S6c; 10–10 to 3 × 10–7 M) were evaluated. Responses to ET-1 (10–7 M) in (–e)EDAs and (–e)EDVs were evaluated after incubation with an ETA receptor antagonist (BQ- 123; 3 × 10–7 M), an ETB receptor antagonist (BQ-788; 3 × 10–7 M), or vehicle solution.

Results—Endothelin-1 induced a concentrationdependent contraction of endothelium-intact and -denuded EDAs and EDVs; EDVs were more sensitive. Neither vessel type relaxed in response to S6c, although 2 of the (–e)EDAs contracted mildly. Whereas BQ-123 inhibited the (–e)EDA and (–e)EDV responses to ET-1, BQ-788 had no effect.

Conclusions and Clinical Relevance—Endothelin-1 induced digital vasoconstriction (marked constriction in veins). This action was unaffected by endothelium and mediated predominantly by ETA receptors. These findings suggest ET-1 can induce selective digital venoconstriction. (Am J Vet Res 2003;64:1438–1443