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 ETA-mediated action or to a shift in the balance between opposing, contractile (ETA-mediated) and relaxant (ETB-mediated), actions. Experiments were performed with isolated ductal strips from preterm (0.7 gestation) and near-term fetal lambs. ET-I 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 ETB antagonist BQ788 (1 muM). 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 ETA receptors. Hence, the concept of ET-1 mediating the oxygen contraction is further validated. Peculiarly, the ET-I contraction is curtailed by light through a hitherto undefined ETB receptor-linked process. (C) 2002 Elsevier Science Inc. All rights reserved.