In vitro oxygen exposure promotes maturation of the oxygen sensitive contraction in pre-term chicken ductus arteriosus

Abstract

The ductus arteriosus (DA) are O2-sensitive, embryonic blood vessels that serve as a right-to-left shunt in developing avian embryos. Prior to internal pipping, the chicken DA produces a weak O2-induced contraction. During hatching, the O2-sensitivity of the avian DA vessels increases significantly. To see if we could accelerate the maturation of chicken DA O2-sensitivity, we exposed the vessel in vitro to elevated O2 (25kPa) for 3-h prior to internal pipping on day 19 of incubation. The DA initially responded to increasing O2 with a weak contraction (0.15±0.04N/m) that significantly increased in strength (0.63±0.06N/m) during 3-h 25kPa O2 exposure. A tonic influence of nitric oxide, not present at low O2, appeared during the 3-h 25kPa O2 exposure. The long-term O2-induced contraction was mediated by both L-type Ca2+ channels and internal Ca2+ stores. The Rho-kinase pathway inhibitors Y-27632 and fasudil produced significant relaxation, suggesting a role for Ca2+ sensitization in the contractile response to the 3h of elevated O2. While the day 19 DA initially exhibited an immature contractile response to O2, maturation of the pathways regulating O2-induced contraction was accelerated by exposure to 25kPa O2, producing contractions similar in magnitude to those found during the final stage of hatching. This suggests that maturation of O2-sensitivity may be accelerated in vivo by increasing arterial O2 levels.