Effects of an endothelin receptor antagonist and nitroglycerin on digital vascular function in horses during the prodromal stages of carbohydrate overload-induced laminitis.
Authors: Eades, Stokes, Moore
Journal: American journal of veterinary research
Summary
# Editorial Summary During the prodromal phase of carbohydrate overload (CHO)-induced laminitis, digital vascular dysfunction develops through a cascade of haemodynamic changes that may be amenable to pharmacological intervention—specifically, endothelin receptor antagonism and nitric oxide donation. Eades and colleagues induced laminitis in 20 horses via nasogastric CHO administration whilst measuring digital arterial haemodynamics in isolated perfused digits under anaesthesia, comparing saline controls against endothelin (ET) receptor antagonist treatment, with nitroglycerin applied to all groups during the experimental protocol. The CHO insult significantly reduced digital blood flow and elevated both total and postcapillary resistances; notably, ET receptor antagonist administration produced reductions in total resistance and specifically in postcapillary resistance, whereas nitroglycerin reduced total resistance but had no effect on postcapillary resistance. These findings suggest that endothelin-mediated vasoconstriction (particularly at the postcapillary level) underpins the vascular dysfunction seen in early CHO-induced laminitis, implicating different mechanisms of action for each therapeutic approach. Whilst conducted in an isolated digit model rather than clinical disease, these results provide mechanistic justification for investigating ET antagonism and nitrates as potential adjunctive treatments during the critical prodromal window when vascular compromise precedes structural laminar failure.
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Practical Takeaways
- •Endothelin receptor antagonists and nitroglycerin may help restore digital vascular function during early stages of carbohydrate overload-induced laminitis, potentially improving clinical outcomes
- •ET receptor antagonists appear more effective than nitroglycerin alone for addressing postcapillary resistance changes in laminitis pathophysiology
- •These findings support therapeutic interventions targeting vascular dysfunction as a mechanism to prevent or reduce severity of laminitis in horses with dietary accidents or grain overload
Key Findings
- •Carbohydrate overload caused significant decrease in digital blood flow with increased total and postcapillary vascular resistances in isolated perfused digits
- •Endothelin receptor antagonist treatment significantly decreased total and postcapillary resistance in CHO-induced laminitis
- •Nitroglycerin treatment significantly decreased total resistance but did not alter postcapillary resistance
- •Combined ET receptor antagonist and nitroglycerin therapy resulted in significant improvement in vascular resistance parameters during prodromal laminitis