Endothelin mediated contraction of equine laminar veins.
Authors: Keen J A, Hillier C, McGorum B C, Nally J E
Journal: Equine veterinary journal
Summary
Endothelin-1 (ET-1) has been implicated as a critical mediator in laminitis pathogenesis, yet the specific vascular mechanisms involved in the equine foot remain poorly understood. Using wire myography on small laminar veins (150–500 micrometres) collected post-mortem from healthy horses and ponies, Keen and colleagues systematically characterised how ET-1 receptor subtypes modulate venous contraction by applying selective receptor antagonists and nitric oxide synthase inhibitors. The ETA receptor proved the dominant driver of ET-1-induced venoconstriction, whilst ETB receptors produced a counterbalancing relaxant effect mediated through nitric oxide; when nitric oxide signalling was blocked, ETB receptor activation alone caused approximately 30% of the contractile force seen with ET-1. These findings reveal a complex balance between constrictor and dilator pathways in laminar circulation during health, suggesting that disruption of this equilibrium—particularly loss of the protective ETB-mediated relaxation—could underpin the microvascular dysfunction characteristic of laminitis. Extending this work to diseased tissue is essential for understanding whether therapeutic strategies targeting ET-1 receptor selectivity might prevent or reverse laminar ischaemia in acute and chronic laminitis cases.
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Practical Takeaways
- •Endothelin-1 dysregulation may be a treatable target in laminitis; understanding normal ET-1 receptor physiology in healthy feet provides a baseline for studying diseased tissue
- •The balance between ETA (contractile) and ETB (dilatory) receptor effects suggests therapeutic modulation of either receptor subtype alone could have unintended consequences on laminar blood flow
- •Further research in laminitic horses is critical before any clinical interventions targeting ET-1 receptors can be recommended for acute or chronic laminitis management
Key Findings
- •ETA receptors mediate endothelin-1 contraction of equine laminar veins; ETB receptor antagonist BQ788 alone had no effect on ET-1-induced contraction
- •ETB receptors on vascular endothelium cause vasodilation via nitric oxide release, opposing the contractile effects of ETA receptors
- •Blocking nitric oxide synthase with L-NAME enhanced ET-1 sensitivity 4-fold and revealed previously masked ETB-mediated smooth muscle contraction (~30% of ET-1 efficacy)
- •Dual ETA and ETB receptor involvement suggests ET-1 effects in healthy laminar veins represent a balance between opposing contractile and dilatory mechanisms