The endothelin ETB receptor antagonist BQ-788 reduces the pulmonary vasodilator effect of endothelin-1 during acute hypoxia in pigs.

Pigs were subjected to acute, intermittent hypoxia (fraction of inhaled O2 0.1, n = 10). The increase in mean pulmonary artery pressure during hypoxia was not altered after i.v. administration of the selective endothelin ETB receptor antagonist BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1- methoxycarbonyltryptophanyl-D-norleucine) (1 mg). However, the vasodilatory effect of endothelin-1 (25 ng/kg per min) infused into the pulmonary artery during hypoxia was attenuated by BQ-788. The present results suggest that the pulmonary vasodilator effect of exogenously administered endothelin-1 during acute hypoxia is mediated by endothelin ETB receptors in the pig. Furthermore, endothelin ETB receptor antagonism with BQ-788 does not influence the pulmonary vascular response to acute hypoxia.