Endothelin in the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia

Elevated concentrations of endothelin (ET), a potent endothelium-derived va soactive peptide, have been reported in a number of pathophysiological cond itions associated with pulmonary hypertension, both in the horse and other species. We have previously shown, both in vitro and in vivo, that the pulm onary and systemic vascular response to exogenous ET is mediated predominan tly via ETA receptors, Our hypothesis in the present study was that ET is i nvolved in the equine hypoxic pulmonary vasoconstrictive response to acute hypoxia, In this study, we investigated the effects of a selective ETA rece ptor antagonist on hypoxic pulmonary hypertension in the mature horse. Hors es were exposed to a 10 min period of hypoxia (F1O2 similar to0.11) on 2 oc casions, with and without pretreatment with the selective ETA receptor anta gonist TBC11251 (10 mg/kg bwt i.v.), Hypoxia increased mean pulmonary arter y pressure (PAP) from 18.3 +/- 0.9 (mean +/- s.e. normoxia) to 28.0 +/- 0.8 mmHg (hypoxia) in the session without ETA receptor antagonism. Carotid art erial pressure (CAP) also increased progressively throughout the period of hypoxic challenge and at the end was 153 +/- 5 mmHg (hypoxia) compared to d uring normoxia (140 +/- 5 mmHg), There was no significant overall effect of ETA receptor antagonism on the haemodynamic or ventilatory responses to ac ute 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 si gnificance at 10 min of hypoxia (P = 0.053), In conclusion, this study desc ribes the haemodynamic and ventilatory changes in response to a period of a cute hypoxia in the adult horse. The results do not support a role for ET a s 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.