Abstract
Background and aim: The mammalian ductus arteriosus undergoes alterations in its pharmacological responsiveness with advancing gestational age. Cyclic AMP and cyclic GMP are second messengers involved in the regulation of ductus arteriosus tone. The aim of the present work was to study the ontogeny of cAMP- and cGMP-evoked ductus arteriosus relaxation in the chicken embryo between 0.7 and 0.9 incubation.
Methods: Isolated right ductus arteriosus segments from chicken embryos at day 15 and day 19 of the 21-d incubation were mounted in a myograph for isometric tension recording, bubbled with 0%, 5% or 95% O2/5% CO2. Relaxations induced by acetylcholine (ACh, 0.1 nM-10 mM), the nitric oxide (NO) donor, sodium nitroprusside (SNP, 0.1 nM-30 mM), the adenylate cyclase activator, forskolin (10 microM-0.3 microM) and the beta-adrenergic agonist, isoproterenol (0.1 nM-10 mM), were evaluated during contraction induced by 62,5 mM K+. Some experiments were performed in the presence the NO synthase inhibitor L-NAME (0.3 mM), the soluble guanylate cyclase inhibitor ODQ, (0.1 microM) or the beta-blocker propanolol (0.1 microM).
Results: Relaxations induced by ACh (inhibited by L-NAME and ODQ), SNP (inhibited by ODQ), forskolin, and isoproterenol (inhibited by propanolol) were not significantly different between 15 and 19 days. Forskolin and isoproterenol completely reversed K+-induced contraction, whereas ACh and SNP only caused respectively 40% and 60 % maximal relaxation. Bubbling the organ chamber with 95% O2 instead of 5% O2, reduced the response to ACh and SNP in both groups of age.
Conclusions: The ductus arteriosus of the chicken embryo responded, in vitro, to NO/cGMP- and cAMP-mediated relaxation, without significant developmental changes. cAMP mediated relaxation was more potent than NO/cGMP mediated relaxation. Oxygen tension modulates chicken embryo ductus arteriosus relaxation.
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Ågren, P., Weerden, M., Kessels, C. et al. 4 Response of Chicken Embryo Ductus Arteriosus to NO/Cyclic GMP- and Cyclic AMP-Mediated Relaxation. Pediatr Res 58, 354 (2005). https://doi.org/10.1203/00006450-200508000-00033
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DOI: https://doi.org/10.1203/00006450-200508000-00033