Effect of 8-isoprostaglandin F2α on the newborn rat pulmonary arterial muscle and endothelium

8-Isoprostaglandin F-2alpha (8-iso-PGF(2alpha)) is a bioactive lipid peroxidation product that is a vasoconstrictor at high concentrations. Paradoxically, at lower, and possibly physiological, concentrations, it is a pulmonary vascular muscle's relaxant. Its effects on newborn pulmonary vasculature are unknown. We hypothesized that the pulmonary arterial 8-iso-PGF(2alpha) responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF(2alpha) effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries ( 100 mum) mounted on a myograph. Force after 8-iso-PGF(2alpha) stimulation was greatest in the adult (P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor N-G-nitro-L- arginine methyl ester (L-NAME) (P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A(2) receptor. Whereas 8-iso-PGF(2alpha) induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA(2) mimetic (U-46619; 1 muM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF(2alpha)-induced contraction was abolished by endothelium removal and L-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA(2)/prostaglandin H-2 receptor blocker, 8-iso-PGF(2alpha) induced NO-mediated relaxation, the magnitude of which was greater in the newborn, compared with the adult ( P < 0.01). When exposed to 8-iso-PGF(2α) in vitro, only the newborn lung secreted TxB(2). We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF(2α) induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA(2). This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.