Experiments were carried out in mutant 129/SvEv mice lacking the endothelin-A (ET(A))-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 ET(A) -/- fetuses, unlike that from ET(A) +/+ littermates, contracted marginally to oxygen and ET-1 but responded to a thromboxane analog. In vivo, reduction in ductus lumen was equally pronounced in tracheotonfized ET(A) -/- and ET(A) +/+ newborns. Conversely, no such vessel narrowing was seen in hyperoxic ET(A) -/- fetuses, although it occurred in ETA +/+ littermates. Notwithstanding the uneven behaviour of the ductus in vitro and in vivo, no ET(A) 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).
|Original language||English (US)|
|Journal||Journal of Cardiovascular Pharmacology|
|Issue number||5 SUPPL. 1|
|State||Published - Nov 16 2000|
- Ductus arteriosus
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine