Submitted on January 1, 2008
Accepted on September 17, 2008
Mechanisms mediating the oxygen-induced vasoreactivity of the ductus arteriosus in the chicken embryo
Henry Greyner1 and Edward M. Dzialowski1*
1 Biological Sciences, University of North Texas, Denton, Texas, United States
* To whom correspondence should be addressed. E-mail: edzial{at}unt.edu.
The avian embryo provides a novel model for studying the ductus arteriosus (DA) during the transition from in ovo to ex ovo life. Here we examined the mechanisms regulating the vasoreactivity of the two morphologically distinct portions of the chicken DA (proximal and distal) in response to O2. The O2-induced contraction is redox sensitive and reversed by the reducing agent dithiothreitol and the H2O2 scavenger N-Mercaptopropionylglycine. As in the mammalian DA, inhibiting mitochondrion derived reactive oxygen species production with rotenone and antimycin A relaxed the O2-constricted DA. The contractile response to O2 matures during hatching and is mimicked by Kv channel inhibitor 4-aminopyridine (4-AP) on day 19 and EP. Together O2 and 4-AP significantly increase DA tone above that observed with either alone. The O2-induced contraction is mediated by influx of extracellular Ca2+ through L-type Ca2+ and store operated channels. IP3 sensitive Ca2+ stores play a minor role in the O2-induced contraction. The O2-induced contraction is mediated by the Rho kinase pathway as fasudil and Y-27632 significantly relax the O2 contracted DA. Prostaglandins E2, F2
, and D2 produce significant contraction of the proximal DA. The O2-induced relaxation of the distal portion of the DA is mediated by an endothelial derived NO/cGMP pathway. Both ODQ and endothelial cells removal inhibit the O2-induced relaxation in the distal segment. The mechanisms regulating O2-induced contraction in the chicken proximal DA are similar to those found in the mammalian DA, making the chicken a useful model for studying the development of this O2-sensitive vessel.
