The response of the lamb ductus arteriosus to endothelin: developmental changes and influence of light.
Endothelin-1 (ET-1) is a putative messenger of oxygen in the ductus arteriosus. Since the ability of the vessel to contract to oxygen increases with gestation, we wished to ascertain whether ET-1 action is also developmentally regulated. A corollary objective was to assess whether any gestational variation in the ET-1 contraction is due to a change in the ET(A)-mediated action or to a shift in the balance between opposing, contractile (ET(A) - mediated) and relaxant (ET(B)-mediated), actions. Experiments were performed with isolated ductal strips from preterm (0.7 gestation) and near-term fetal lambs. ET-1 contracted the ductus dose-dependently (10(-10)-10(-7) M) at both ages; however, the peak contraction was about double in magnitude at term. Regardless of age, ET-1 contraction was greater with preparations kept in the dark compared to those exposed to light. This effect of light was not seen after removing the endothelium or when treating the intact tissue with the ET(B) antagonist BQ788 (1 microM). In the dark, however, BQ788 did not modify significantly the ET-1 response at either age. We conclude that ET-1 becomes a stronger ductus constrictor with fetal age, conceivably by acting on ET(A) receptors. Hence, the concept of ET-1 mediating the oxygen contraction is further validated. Peculiarly, the ET-1 contraction is curtailed by light through a hitherto undefined ET(B) receptor-linked process.
Coceani
Flavio
F
Integrative Biology Programme, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada. coceani@sssup.it
Kelsey
Lois
L
Seidlitz
Eric
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000196:embryology / Q000528:radiation effects; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008027:Light; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011247:Pregnancy; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects; D012756:Sheep
D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)