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

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 Popullation - 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 30°C. 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 concentration-dependent 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.