New mediators in the biology of the ductus arteriosus: Lessons from the chicken embryo

The chicken embryo is an ideal model for the study of new hypotheses on the developmental biology of ductus arteriosus (DA). A unique characteristic of chicken DA is that it is the result of the fusion of two vessels with different embryological origins, morphologies, and functionalities. The pulmonary side (PulmDA) consists almost exclusively of neural crest-derived cells, shows the structure of a muscular artery, and responds to O2 with contraction whereas the aortic part is of mesodermal origin, shows the morphology of an elastic artery and relaxes in response to O2. In addition the two parts of the DA show marked differences in responsiveness to other contractile and relaxant agents. In mammals, the most accepted model of O2-induced DA constriction involves a rise in O2 modulating the function of the mitochondrial electron transport chain (the sensor), leading to an increased production of H2O2 (the mediator) that causes the inhibition of KV channels (the effector) with Rho kinase acting as another downstream effector of the O2-sensing system in the DA. In the chicken embryo, we verified the very same pathway, proving a conserved mechanism for O2 sensing/signaling in mammalian and nonmammalian DA. Moreover, we demonstrated a developmentally regulated response to O2, which is restricted to the mature PulmDA and involves parallel maturation of the three components: sensor, mediator, and effectors. Besides O2, we used the chicken embryo model to investigate the possible ductal effects of vasoactive mediators such as ceramide, H2S, isoprostanes, or platelet-derived vasoactive mediators.