title: Deletion of the endothelin-A-receptor suppresses oxygen-induced constriction but not postnatal closure of the ductus arteriosus.
abstract: 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 tracheotomized ET(A) -/- and ET(A) +/+ newborns. Conversely, no such vessel narrowing was seen in hyperoxic ET(A), -/- fetuses, although it occurred in ET(A) +/+ 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).
authors.affiliation: Integrative Biology Programme, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Coceani
authors.forename: Y A
authors.initials: YA
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Seidlitz
authors.forename: L
authors.initials: L
authors.lastname: Kelsey
authors.forename: T
authors.initials: T
authors.lastname: Kuwaki
authors.forename: C
authors.initials: C
authors.lastname: Ackerley
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
mesh_terms: D000818:Animals; D004373:Ductus Arteriosus / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D010100:Oxygen