Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus

Abstract

Prostaglandin E2 (PGE2) is the major vasodilator prostanoid of the mammalian ductus arteriosus (DA). In the present study we analyzed the response of isolated DA rings from 15-, 19- and 21-day-old chicken embryos to PGE2 and other vascular smooth muscle relaxing agents acting through the cyclic AMP signaling pathway. PGE2 exhibited a relaxant response in the 15-day DA, but not in the 19- and 21-day DA. Moreover, high concentrations of PGE2 (3 μM in 15-day and 1 μM in 19-day and 21-day DA) induced contraction of the chicken DA. The presence of the TP receptor antagonist SQ29,548, unmasked a relaxant effect of PGE2 in the 19- and 21-day DA and increased the relaxation induced by PGE2 in the 15-day DA. The presence of the EP receptor antagonist AH6809 abolished PGE2-mediated relaxation. The relaxant responses induced by PGE 2 and the β-adrenoceptor agonist isoproterenol, but not those elicited by the adenylate cyclase activator forskolin or the phosphodiesterase 3 inhibitor milrinone, decreased with maturation. High oxygen concentrations (95%) decreased the relaxation to PGE2. The relaxing potency and efficacy of isoproterenol and milrinone were higher in the pulmonary than in the aortic side of the DA, whereas no regional differences were found in the response to PGE2. We conclude that, in contrast to the mammalian situation, PGE2 is a weak relaxant agent of the chicken DA and, with advancing incubation, it even stimulates TP vasoconstrictive receptors.