PI: Edward M. Dzialowski, University of North Texas

The ductus arteriosus plays a critical role during embryonic development of tetrapod vertebrates, but it must close shortly after initiation of lung ventilation so that neonatal metabolism can be fully supported. In developing mammals and birds, the ductus arteriosi provides a right-to-left shunt of blood away from the high resistance pulmonary circuit to the lower resistance systemic circuit, ensuring that the developing animal has adequate blood flow to the embryonic gas exchanger. In contrast to the mammalian fetus with a single ductus arteriosus, the developing avian embryo has two ductus arteriosi that allow for this shunt of blood. In the bird, the right and left ductus arteriosi connect the right and left pulmonary arteries to the aorta to form the descending aorta. Upon the initiation of lung ventilation, the ductus arteriosi of both groups begins to constrict. Hatching and the constriction of the right and left ductus arteriosi lasts roughly 20 to 30 hours in the chicken and emu, up to ten times longer than most mammals. The prolonged time it takes the avian ductus arteriosi to close makes the developing bird embryo an exciting model for studying the regulation of ductus vessel tone during the transition to lung ventilation. The long-term goal is to understand the mechanisms regulating in vivo avian ductus arteriosi tone from the embryonic stage through hatching and to use the avian model to understand the influence of environmental and pharmacological stressors on ductus arteriosi function prior to, during, and after initiation of lung ventilation. The specific goals of the proposed research are to examine the role of oxygen, prostaglandins, and nitric oxide in regulating avian ductus arteriosi tone through development and determine the timing of the functional and anatomical closure of the avian ductus arteriosi. This study provides the first comprehensive examination of the physiology of a non-mammalian ductus arteriosus and insight into the mechanisms involved in avian cardiovascular regulation during the transition to ex ovo life. The research proposed here is a necessary step toward discovering the factors regulating avian ductus arteriosi tone in vivo during hatching and will expand the role of the avian embryo as a model system in developmental cardiovascular physiology. This project will train a diverse group of undergraduate and graduate level students in the emerging field of developmental physiology. Finally, local high school biology teachers will participate in summer research and take the experience back into their classrooms.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Type
Standard Grant (Standard)
Application #
0417205
Program Officer
Michael L. Mishkind
Project Start
Project End
Budget Start
2004-08-01
Budget End
2008-07-31
Support Year
Fiscal Year
2004
Total Cost
$394,062
Indirect Cost
Name
University of North Texas
Department
Type
DUNS #
City
Denton
State
TX
Country
United States
Zip Code
76203