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

Autor: C. R. Pace-Asciak, J. Belik, A. K. Tanswell, Robert P. Jankov, Man Yi, Jingyi Pan
Rok vydání: 2003
Předmět:
Zdroj: Journal of Applied Physiology. 95:1979-1985
ISSN: 1522-1601
8750-7587
DOI: 10.1152/japplphysiol.00420.2003
Popis: 8-Isoprostaglandin F2α (8-iso-PGF2α) 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-PGF2α responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2α effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 μm) mounted on a myograph. Force after 8-iso-PGF2α stimulation was greatest in the adult ( P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) ( P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A2 receptor. Whereas 8-iso-PGF2α induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 μM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2α-induced contraction was abolished by endothelium removal and l-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA2/prostaglandin H2 receptor blocker, 8-iso-PGF2α 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-PGF2α in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2α induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA2. This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.
Databáze: OpenAIRE