Endothelin-1 release from lamb ductus arteriosus: relevance to postnatal closure of the vessel

Can J Physiol Pharmacol. 1991 Feb;69(2):218-21. doi: 10.1139/y91-033.


Our previous investigations have shown that endothelin-1 (ET-1) is a singularly potent constrictor of the ductus arteriosus and that a cytochrome P-450 system located in the sarcolemma is crucial for the contractile response of the vessel to oxygen. We have now studied the release of ET-1 from isolated ductus arteriosus preparations of near-term fetal lambs. Preparations produced measurable amounts of ET-1 under basal conditions (about 0.04 pg/100 mg wet weight.min) both in the presence and absence of the endothelium. Anisomycin (10(-4) M) reduced this release by 50%, while thrombin (1 U/mL) doubled the release. Treatment with a CO mixture (CO/O2 ratio, 0.27) inhibited ET-1 release from intact and endothelium-denuded preparations. We propose that oxygen triggers closure of the ductus arteriosus at birth by causing a conformational change in a specific cytochrome P-450, which, in turn, provides the signal for the synthesis of the constrictor ET-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisomycin / pharmacology
  • Cytochrome P-450 Enzyme System / metabolism
  • Ductus Arteriosus / growth & development
  • Ductus Arteriosus / metabolism*
  • Endothelins / pharmacology*
  • Endothelium, Vascular / physiology
  • Female
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Pregnancy
  • Protein Conformation
  • Sheep


  • Endothelins
  • Iodine Radioisotopes
  • Anisomycin
  • Cytochrome P-450 Enzyme System