Equine pulmonary and systemic haemodynamic responses to endothelin-1 and a selective ET(A) receptor antagonist.
Authors: Benamou A E, Marlin D J, Lekeux P
Journal: Equine veterinary journal
Summary
# Editorial Summary Endothelin-1 (ET-1), an endogenous vasoactive peptide, exerts powerful vasoconstrictive effects on both pulmonary and systemic circulations in horses, mediated primarily through ET(A) receptors—a finding that may help explain the pathophysiology of hypertensive conditions in equine practice. Benamou and colleagues administered escalating intravenous boluses of ET-1 (0.1–0.4 µg/kg) to six conscious, resting horses and measured pulmonary artery pressure (PAP), carotid artery pressure (CAP), cardiac output, and vascular resistance; they then blocked ET(A) receptors pharmacologically to confirm the mechanism. ET-1 produced striking dose-dependent increases in mean PAP (up to 79%) and CAP (up to 51%), whilst simultaneously reducing cardiac output by as much as 35% and doubling systemic vascular resistance; pulmonary vascular resistance also increased, though not significantly. Critically, selective ET(A) receptor antagonism completely abolished these haemodynamic responses, confirming that ET(A) receptors drive the vasoconstriction in both circulations. For equine practitioners, these findings suggest that endothelin dysregulation may contribute to conditions characterised by pulmonary hypertension or systemic hypertension, potentially opening new therapeutic avenues through ET(A) receptor modulation—particularly relevant for horses with exercise-induced pulmonary hypertension or those presenting with signs of circulatory compromise.
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Practical Takeaways
- •Endothelin antagonism may represent a therapeutic target for managing hypertensive conditions in horses, particularly pulmonary hypertension associated with exercise or disease
- •The differential time-course of pulmonary versus systemic vascular responses suggests distinct pathophysiological mechanisms that could inform treatment strategies
- •ET(A) receptor selectivity of vasoconstriction indicates that selective receptor antagonists may be more effective and safer than non-selective endothelin inhibition
Key Findings
- •ET-1 bolus injections (0.1–0.4 µg/kg) caused mean pulmonary artery pressure increases of up to 79% and carotid artery pressure increases of 51% in conscious horses
- •ET-1 decreased cardiac output by up to 35% and increased systemic vascular resistance by up to 104%
- •ET(A) receptor antagonist (TBC11251) completely inhibited haemodynamic responses to subsequent ET-1 challenge, confirming ET(A) receptor mediation
- •ET-1 effects on pulmonary artery pressure were rapid and transient (<10 min), whilst carotid artery pressure effects persisted up to 60 min