Pia Ågren

Morphological and Functional Alterations of the Ductus Arteriosus in a Chicken Model of Hypoxia-Induced Fetal Growth Retardation

The hypoxic conditions in which children with intrauterine growth retardation (IUGR) develop are hypothesized to alter the development of the ductus arteriosus (DA). We aimed to evaluate the effects of in ovo hypoxia on chicken DA morphometry and reactivity. Hypoxia (15% O2 from day 6 to 19 of the 21-d incubation period) produced a reduction in the body mass of the 19-d fetuses and a shortening of right and left DAs. However, ductal lumen and media cross-sectional areas were not affected by hypoxia. The ductal contractions induced by oxygen, KCl, H2O2, 4-aminopyridine, and endothelin-1 were similar in control and hypoxic fetuses. In contrast, the DAs from the hypoxic fetuses showed increased contractile responses to norepinephrine and phenylephrine and impaired relaxations to acetylcholine, sodium nitroprusside, and isoproterenol. The relaxations induced by 8-Br-cGMP, forskolin, Y-27632, and hydroxyfasudil were not altered by chronic hypoxia. In conclusion, chronic in ovo hypoxia-induced growth retardation in fetal chickens and altered the response of the DA to adrenergic agonists and to endothelium-dependent and -independent relaxing agents. Our observations support the concept that prolonged patency of the DA in infants with IUGR may be partially related with hypoxia-induced changes in local vascular mechanisms.

Response of Chicken Ductus Arteriosus to Hypercarbic and Normocarbic Acidosis

Background: Changes in pH can have profound effects on vascular tone and reactivity, but their influence on the ductus arteriosus (DA) remains unknown. Objective: To analyzethe effects of hypercarbic and normocarbic acidosis in the reactivity of the chicken DA. Methods: DA rings from 19-day chicken fetuses (total incubation time, 21 days) were mounted in a wire myograph for isometric tension recording. Results: In DA rings (pulmonary side) stimulated with O2, norepinephrine (NE), KCl, or U46619, changes from control conditions (5% CO2, 24 mM NaHCO3, pH 7.4) to 7.5% CO2 (pH 7.25) or 10% CO2 (pH 7.14) induced a concentration-dependent relaxation that reached 43.0% (SD 21.3) of the O2-, 28.6% (SD 23.1) of the NE-, 10.4% (SD 18.7) of the KCl-, and 6.8% (SD 12.6) of the U46619-induced contraction. Hypercarbic-acidosis-induced relaxation was impaired by the non-selective K+ channel blocker tetraethylammonium or the BKCa channel inhibitor iberiotoxin. Normocarbic acidosis (5% CO2, 12 mM NaHCO3, pH 7.13) induced transient relaxation of the DA, which was not affected by the presence of tetraethylammonium or iberiotoxin. Euhydric hypercarbia (10% CO2, 48 mM NaHCO3, pH 7.46) induced a transient contraction of the DA. Conclusions: Our results indicate that the chicken DA is very sensitive to changes in extracellular pH, and that stimulation of BKCa channels may account for the ductal-relaxing effects of hypercarbic acidosis.