Deletion of the endothelin-A-receptor suppresses oxygen-induced constriction but not postnatal closure of the ductus arteriosus

Experiments were carried out in mutant 129/SvEv mice lacking the endothelin -A (ETA)-receptor to determine whether endothelin-1 (ET-1), acting as a mes senger for oxygen constriction, is responsible for closure of the ductus ar teriosus at birth. The isolated ductus from ETA-/- fetuses, unlike that fro m ETA +/+ littermates, contracted marginally to oxygen and ET-1 but respond ed to a thromboxane analog. In vivo, reduction in ductus lumen was equally pronounced in tracheotomized ETA-/- and ETA +/+ newborns. Conversely, no su ch vessel narrowing was seen in hyperoxic ETA-/- fetuses, although it occur red in ETA +/+ littermates. Notwithstanding the uneven behaviour of the duc tus in vitro and in vivo, no ETA genotype-related difference was noted in t he morphology of the vessel on both light and electron microscopy. We concl ude that ET-1 mediates the ductus constriction to oxygen. Without ET-1, how ever, the vessel still closes postnatally probably as a result of the withd rawal of the relaxing influence of prostaglandin E-2 (PGE(2)).