title: Effect of 8-isoprostaglandin F2alpha on the newborn rat pulmonary arterial muscle and endothelium.
abstract: 8-Isoprostaglandin F2alpha (8-iso-PGF2alpha) 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-PGF2alpha responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2alpha effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 microm) mounted on a myograph. Force after 8-iso-PGF2alpha 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-PGF2alpha induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 microM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2alpha-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-PGF2alpha 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-PGF2alpha in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2alpha 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.
authors.affiliation: Canadian Institutes of Health Research Group in Lung Development, Lung Biology and Integrative Biology Programmes, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada. Jaques.Belik@SickKids.ca
authors.forename: J
authors.initials: J
authors.lastname: Belik
authors.forename: R P
authors.initials: RP
authors.lastname: Jankov
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: M
authors.initials: M
authors.lastname: Yi
authors.forename: C R
authors.initials: CR
authors.lastname: Pace-Asciak
authors.forename: A K
authors.initials: AK
authors.lastname: Tanswell
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: C117466:8-isoprostaglandin A2; D004791:Enzyme Inhibitors; D011454:Prostaglandins A; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019331:NG-Nitroarginine Methyl Ester