Contractile and relaxing mechanisms in pulmonary resistance arteries of the preterm fetal lamb

Isolated pulmonary resistance arteries from term fetal lambs have nitric ox ide (NO)- and prostaglandin-mediated relaxing mechanisms which are activate d when PO2 is raised from fetal to neonatal levels. The same vessels contra ct 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 c orrelates with the development of susceptibility to oxygen changes. Experim ents were carried out at neonatal PO2, when expectedly relaxing mechanisms are maximally expressed, or under hypoxia. At either fetal age, the NO synt hesis inhibitor, N-G-nitro-L-arginine methyl ester (100 mu M), had no effec t on basal tone, while indomethacin (2.8 mu M) was a weak constrictor. Prem ature arteries did not contract when first exposed to hypoxia, but they res ponded marginally to a second exposure. The same arteries contracted strong ly to a thromboxane A(2) analogue (ONO-11113, 0.1 mu M) and ET-1 (10 nM), w hile their contraction to activating solution (5 mM Ca2+ in K+-Krebs soluti on) was small and variable. At 0.7 gestation, bradykinin (0.1-100 nM), acet ylcholine (0.01-10 mu M), and sodium nitroprusside (0.1 nM to 10 mu M) 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 arter ies have viable effector mechanisms for contraction and relaxation. However , the capability for these mechanisms to be activated by PO2 changes is mar kedly curtailed. Copyright (C) 2000 S. Karger AG, Basel.