Effect of 8-isoprostaglandin F 2α on the newborn rat pulmonary arterial muscle and endothelium

• Published in: Journal of applied physiology (1985) 2003-11, Vol.95 (5), p.1979-1985
• Main Authors: Belik, J., Jankov, R. P., Pan, J., Yi, M., Pace-Asciak, C. R., Tanswell, A. K.
• Format: Article
• Language: English
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00420.2003

8-Isoprostaglandin F 2α (8-iso-PGF 2α ) 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 2α responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF 2α effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 μm) mounted on a myograph. Force after 8-iso-PGF 2α 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 2α induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA 2 mimetic (U-46619; 1 μM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF 2α -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 2α 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.