Endothelin in the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia.
Authors: Benamou A E, Marlin D J, Lekeux P
Journal: Equine veterinary journal
Summary
# Editorial Summary: Endothelin and Hypoxic Pulmonary Vasoconstriction in Horses When horses experience acute hypoxia, their pulmonary arteries constrict to maintain ventilation–perfusion matching—a protective reflex called hypoxic pulmonary vasoconstriction (HPV). Benamou and colleagues investigated whether endothelin (ET), a potent vasoactive peptide known to contribute to pulmonary hypertension in various disease states, drives this response by administering a selective ET(A) receptor antagonist (TBC11251, 10 mg/kg i.v.) to mature horses before exposing them to severe hypoxia (approximately 11% inspired oxygen for 10 minutes). Hypoxia reliably elevated mean pulmonary artery pressure from 18.3 ± 0.9 mmHg at rest to 28.0 ± 0.8 mmHg, with corresponding increases in systemic pressure, yet blocking ET(A) receptors produced no significant effect on these haemodynamic or ventilatory responses—though a trend emerged between 5–10 minutes that approached statistical significance (P = 0.053). The findings suggest that whilst ET may modulate HPV or contribute to more prolonged hypoxic responses, it is not the primary acute mediator in healthy horses, implying that other mechanisms such as direct oxygen sensing or alternative vasoactive pathways dominate the initial reflex. For practitioners managing horses with respiratory compromise, this work tempers expectations about ET antagonism as a standalone therapeutic target for acute hypoxia, though it leaves open the possibility of ET involvement in chronic or progressive pulmonary hypertension scenarios.
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Practical Takeaways
- •Endothelin receptor antagonism does not appear to be an effective therapeutic target for acute hypoxic pulmonary hypertension in horses under short-term hypoxic stress
- •Endothelin may play a modulatory role in prolonged (>10 min) hypoxic pulmonary vasoconstriction rather than the initial acute response, suggesting different pathophysiological mechanisms occur at different time points
- •Current understanding suggests acute HPV in horses is mediated by mechanisms independent of ET(A) receptors, limiting the applicability of ET-antagonist therapies for conditions involving brief hypoxic episodes
Key Findings
- •Acute hypoxia (FIO2 0.11 for 10 min) increased mean pulmonary artery pressure from 18.3 to 28.0 mmHg in horses
- •Selective ET(A) receptor antagonist TBC11251 showed no significant overall effect on haemodynamic or ventilatory responses to acute hypoxia
- •Between 5-10 min of hypoxia, mean PAP showed a trend toward divergence between treatment groups (P=0.053), suggesting endothelin may modulate slower phases of hypoxic pulmonary vasoconstriction rather than acute response