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 (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).
Coceani
F
F
Integrative Biology Programme, The Hospital for Sick Children, Toronto, Ontario, Canada.
Liu
Y A
YA
Seidlitz
E
E
Kelsey
L
L
Kuwaki
T
T
Ackerley
C
C
Yanagisawa
M
M
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*
D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D010100:Oxygen