Ontogeny of chicken ductus arteriosus response to oxygen and vasoconstrictors

1 Department of Pediatrics, Maastricht University Hospital, Research Institute Growth and Development (GROW), University of Maastricht, Maastricht; 2 Department of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, Madrid, Spain; and 3 Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands Submitted 21 March 2006 ; accepted in final form 7 August 2006 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, noninternally-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 O 2 (0 to 21%), norepinephrine (NE), or phenylephrine (Phe) but contracted in response to high-K + solution, the inhibitor of voltage-gated channels 4-aminopyridine, U-46619, and endothelin (ET)-1. These responses increased with advancing incubation age. Contractile responses to O 2 , 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 N -nitro- L -arginine methyl ester and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and reduced by the peptidic ET A and ET B -receptor antagonist PD-142,893. Transmural electrical stimulation of nerves, the nonselective cyclooxygenase (COX) inhibitor indomethacin, the COX-1 inhibitor valeryl salicylate, the COX-2 inhibitor nimesulide, the inhibitor of ATP-sensitive K + channels glibenclamide, and the inhibitor of Ca 2+ -activated K + 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 O 2 and cathecolamines appear later in development and are located in the pulmonary side of the DA. ductus arteriosus; chicken embryo; potassium channels; oxygen sensing; cathecolamines Address for reprint requests and other correspondence: E. Villamor. Dept of Pediatrics, Univ. Hospital Maastricht, P. Debyelaan 25. P.O. Box 580