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J Appl Physiol 95: 1979-1985, 2003. First published July 11, 2003; doi:10.1152/japplphysiol.00420.2003
8750-7587/03 $5.00
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Effect of 8-isoprostaglandin F2{alpha} on the newborn rat pulmonary arterial muscle and endothelium

J. Belik,1 R. P. Jankov,1 J. Pan,1 M. Yi,1 C. R. Pace-Asciak,2 and A. K. Tanswell1

1Canadian Institutes of Health Research Group in Lung Development, Lung Biology and Integrative Biology Programmes, Hospital for Sick Children Research Institute, and 2Departments of Pediatrics, Pharmacology and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Submitted 28 April 2003 ; accepted in final form 8 July 2003

8-Isoprostaglandin F2{alpha} (8-iso-PGF2{alpha}) 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-PGF2{alpha} responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2{alpha} effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 µm) mounted on a myograph. Force after 8-iso-PGF2{alpha} 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-PGF2{alpha} 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-PGF2{alpha}-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-PGF2{alpha} 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-PGF2{alpha} in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2{alpha} 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.

isoprostanes; reactive oxygen species; endothelin-1; antioxidants; cyclooxygenase; 8-isoprostaglandin F2{alpha}


Address for reprint requests and other correspondence: J. Belik, University of Toronto, Div. of Neonatology, Hospital for Sick Children, Rm. 3886, 555 University Ave., Toronto, ON, Canada M5G 1X8 (E-mail: Jaques.Belik{at}SickKids.ca).




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