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

F. Coceani, Y. A. Liu, E. Seidlitz, L. Kelsey, T. Kuwaki, C. Ackerley, M. Yanagisawa

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 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 languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume36
Issue number5 SUPPL. 1
StatePublished - 2000

Fingerprint

Ductus Arteriosus
Endothelin A Receptors
Endothelins
Constriction
Endothelin-1
Oxygen
Fetus
129 Strain Mouse
Thromboxanes
Dinoprostone
Electron Microscopy
Genotype
Parturition
Light

Keywords

  • Ductus arteriosus
  • Endothelin
  • Oxygen

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Deletion of the endothelin-A-receptor suppresses oxygen-induced constriction but not postnatal closure of the ductus arteriosus. / Coceani, F.; Liu, Y. A.; Seidlitz, E.; Kelsey, L.; Kuwaki, T.; Ackerley, C.; Yanagisawa, M.

In: Journal of Cardiovascular Pharmacology, Vol. 36, No. 5 SUPPL. 1, 2000.

Research output: Contribution to journalArticle

Coceani, F. ; Liu, Y. A. ; Seidlitz, E. ; Kelsey, L. ; Kuwaki, T. ; Ackerley, C. ; Yanagisawa, M. / Deletion of the endothelin-A-receptor suppresses oxygen-induced constriction but not postnatal closure of the ductus arteriosus. In: Journal of Cardiovascular Pharmacology. 2000 ; Vol. 36, No. 5 SUPPL. 1.
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