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Am J Physiol Regul Integr Comp Physiol 295: R1647-R1659, 2008. First published September 17, 2008; doi:10.1152/ajpregu.00001.2008
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COMPARATIVE AND EVOLUTIONARY PHYSIOLOGY

Mechanisms mediating the oxygen-induced vasoreactivity of the ductus arteriosus in the chicken embryo

Henry Greyner and Edward M. Dzialowski

Department of Biological Science, University of North Texas, Denton, Texas

Submitted 1 January 2008 ; accepted in final form 17 September 2008

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. Oxygen-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 the Kv channel inhibitor 4-aminopyridine (4-AP) on day 19 and externally pipped (EP) embryos. 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. Inositol 1,4,5-trisphosphate-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{alpha}, 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 nitric oxide/cGMP pathway. Both 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and endothelial cell removal inhibit O2-induced relaxation in the distal segment. Mechanisms regulating O2-induced contraction in chicken proximal DA are similar to those found in mammalian DA, making the chicken a useful model for studying development of this O2-sensitive vessel.

oxygen; calcium L-channels; store-operated channels; Rho kinase; reactive oxygen species


Address for reprint requests and other correspondence: E. M. Dzialowski. Dept. of Biological Sciences. Univ. of North Texas, 1155 Union Circle #305220, Denton, TX 76203-5017 (e-mail: edzial{at}unt.edu)






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