title: Contractile and relaxing mechanisms in pulmonary resistance arteries of the preterm fetal lamb.
abstract: Isolated pulmonary resistance arteries from term fetal lambs have nitric oxide (NO)- and prostaglandin-mediated relaxing mechanisms which are activated when PO(2) is raised from fetal to neonatal levels. The same vessels contract under hypoxia, and the contraction has been ascribed to endothelin-1 (ET-1). We have now studied these vasoeffector mechanisms before term (0.7 and 0.65 gestation) with the objective of determining whether their activity correlates with the development of susceptibility to oxygen changes. Experiments were carried out at neonatal PO(2), when expectedly relaxing mechanisms are maximally expressed, or under hypoxia. At either fetal age, the NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (100 microM), had no effect on basal tone, while indomethacin (2.8 microM) was a weak constrictor. Premature arteries did not contract when first exposed to hypoxia, but they responded marginally to a second exposure. The same arteries contracted strongly to a thromboxane A(2) analogue (ONO-11113, 0.1 microM) and ET-1 (10 nM), while their contraction to activating solution (5 mM Ca(2+) in K(+)-Krebs solution) was small and variable. At 0.7 gestation, bradykinin (0.1-100 nM), acetylcholine (0.01-10 microM), and sodium nitroprusside (0.1 nM to 10 microM) dose-dependently relaxed arteries precontracted with ONO-11113. Conversely, at 0.65 gestation the relaxation to bradykinin and acetylcholine was not dose-dependent and tended to be weaker. We conclude that preterm pulmonary arteries have viable effector mechanisms for contraction and relaxation. However, the capability for these mechanisms to be activated by PO(2) changes is markedly curtailed.
authors.affiliation: Integrative Biology Programme, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Y A
authors.initials: YA
authors.lastname: Liu
authors.forename: J G
authors.initials: JG
authors.lastname: Theis
authors.forename: F
authors.initials: F
authors.lastname: Coceani
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000196:embryology*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin