Elevated concentrations of
endothelin (ET), a potent endothelium-derived vasoactive
peptide, have been reported in a number of pathophysiological conditions associated with
pulmonary hypertension, both in the horse and other species. We have previously shown, both in vitro and in vivo, that the pulmonary and systemic vascular response to exogenous ET is mediated predominantly via ET(A) receptors. Our hypothesis in the present study was that ET is involved in the equine hypoxic pulmonary vasoconstrictive response to acute
hypoxia. In this study, we investigated the effects of a selective ET(A) receptor antagonist on hypoxic
pulmonary hypertension in the mature horse. Horses were exposed to
a 10 min period of
hypoxia (F(I)O2 approximately 0.11) on 2 occasions, with and without pretreatment with the selective ET(A) receptor antagonist
TBC11251 (10 mg/kg bwt i.v.).
Hypoxia increased mean pulmonary artery pressure (PAP) from 18.3+/-0.9 (mean +/- s.e. normoxia) to 28.0+/-0.8 mmHg (
hypoxia) in the session without ET(A) receptor antagonism. Carotid arterial pressure (CAP) also increased progressively throughout the period of hypoxic challenge and at the end was 153+/-5 mmHg (
hypoxia) compared to during normoxia (140+/-5 mmHg). There was no significant overall effect of ET(A) receptor antagonism on the haemodynamic or ventilatory responses to acute
hypoxia. However, between 5 and 10 min of
hypoxia there was a trend for the mean PAP to diverge in the 2 treatments, which just failed to reach significance
at 10 min of
hypoxia (P = 0.053). In conclusion, this study describes the haemodynamic and ventilatory changes in response to a period of acute
hypoxia in the adult horse. The results do not support a role for ET as a mediator of acute HPV in the horse, but suggest that it may be involved as a modulator or in the slower (>10 min) phase of HPV.