Equine pulmonary and systemic haemodynamic responses to endothelin-1 and a selective ET(A) receptor antagonist.
Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ET(A) receptors. Pulmonary and systemic haemodynamic responses to endothelin-1 (ET-1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET-1 (0.1, 0.2 and 0.4 microg/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respectively. The effect of ET-1 on PAP and CAP was rapid and transient for PAP (-10 min) but prolonged for CAP (up to 60 min). ET-1 significantly decreased cardiac output by up to 35% and significantly increased systemic vascular resistance (SVR) by up to 104%. Pulmonary vascular resistance (PVR) showed a trend (P>0.05) to increase with 0.2 and 0.4 microg/kg bwt ET-1. Infusion of a selective ET(A) receptor antagonist (TBC11251) completely inhibited the responses to a subsequent bolus of 0.2 microg/kg bwt ET-1. We conclude that exogenous ET-1 exerts a potent vasoconstrictive action on the pulmonary and systemic circulations of the horse. These effects appear to be mediated largely through ET(A) receptors in both circulations. Endothelin may play a role in hypertensive conditions in the horse.
Benamou
A E
AE
Centre for Equine Studies, Animal Health Trust, Kentford, Newmarket, UK.
Marlin
D J
DJ
Lekeux
P
P
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006736:Horses / Q000502:physiology*; D007275:Injections, Intravenous / Q000662:veterinary; D007555:Isoxazoles / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D044022:Receptor, Endothelin A; D013876:Thiophenes / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007555:Isoxazoles; D044022:Receptor, Endothelin A; D013876:Thiophenes; D014662:Vasoconstrictor Agents; C106276:sitaxsentan