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1 Pediatrics, Maastricht University Hospital, Maastricht, Netherlands
2 Pediatrics, Maastricht University Hospital, Maastricht, Netherlands; Dept. Pharmacology, School of Medicine, Madrid, Spain
3 Dept. Pharmacology, School of Medicine, Madrid, Spain
4 Pharmacology & Toxicology, Universiteit Maastricht, Maastricht, Netherlands
* To whom correspondence should be addressed. E-mail: eiv{at}paed.azm.nl.
The present study aimed to characterize the contractile reactivity of the chicken ductus arteriosus (DA) from the last stage of prenatal development and throughout the perinatal period. Isolated DA rings from 15-day, non-internally-pipped 19-day, and externally-pipped 21-day embryos were studied using myograph techniques. On embryonic day 15, the chicken DA did not respond to O2(0 to 21%), norepinephrine (NE), or phenylephrine (Phe) but contracted in response to high-K+ solution, the inhibitor of KV channels 4-aminopyridine, the thromboxane A2mimetic U46619, and endothelin-1 (ET-1). These responses increased with advancing incubation age. Contractile responses to O2, NE and Phe were present in the 19 and 21-day embryo. Oxygen-induced contraction was restricted to the pulmonary side of the DA and was augmented by the nitric oxide synthase inhibitor L-NAME and the soluble guanylate cyclase inhibitor ODQ and reduced by the peptidic ETA and ETB-receptor antagonist PD 142,893. Transmural electrical stimulation of nerves, the non-selective cyclooxygenase (COX) inhibitor indomethacin, the COX-1 inhibitor valeryl salicylate, the COX-2 inhibitor nimesulide, the inhibitor of KATP channels glibenclamide, and the inhibitor of KCa channels tetraethylammonium did not cause contraction of the DA rings at any age. We conclude that transition to ex ovo life is accompanied by dramatic changes in chicken DA reactivity. At 0.7 incubation, excitation-contraction and pharmacomechanical coupling for several contractile agonists are already present, whereas the constrictor effects of O2 and cathecolamines appear later in development and are located in the pulmonary side of the DA.
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