Deletion of the Endothelin-A-Receptor Suppresses Oxygen-Induced Constriction but not Postnatal Closure of the Ductus Arteriosus

Summary: 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 messenger for oxygen constriction, is responsible for closure of the ductus arteriosus at birth. The isolated ductus from ETA −/− fetuses, unlike that from ETA +/+ littermates, contracted marginally to oxygen and ET-1 but responded to a thromboxane analog. In vivo, reduction in ductus lumen was equally pronounced in tracheotomized ETA −/− and ETA +/+ newborns. Conversely, no such vessel narrowing was seen in hyperoxic ETA −/− fetuses, although it occurred in ETA +/+ littermates. Notwithstanding the uneven behaviour of the ductus in vitro and in vivo, no ETA genotype-related difference was noted in the morphology of the vessel on both light and electron microscopy. We conclude that ET-1 mediates the ductus constriction to oxygen. Without ET-1, however, the vessel still closes postnatally probably as a result of the withdrawal of the relaxing influence of prostaglandin E2 (PGE2).