RELAXING AND CONTRACTILE MECHANISMS IN RESISTANCE PULMONARY ARTERIES IN THE PREMATURE FETAL LAMB † 1603

Isolated pulmonary resistance arteries from term fetal lamb have nitric oxide (NO)- and prostaglandin (PG)-based relaxing mechanisms which are activated upon raising PO₂ from fetal (22 mmHg) to neonatal (65 mmHg) levels. The same vessels contract when PO₂is lowered to about 10 mmHg, and the response has been ascribed to endothelin-1 (ET-1) formation. We have now studied these arteries at 0.7 gestation. Inhibition of PG (indomethacin 2.8 μM) and NO (L-NAME 100 μM) synthesis marginally contracted arteries(respectively, 0.09±0.02 mN/mm and 0.09±0.03 mN/mm; n=9 for both) at neonatal PO₂. Similarly weak was the hypoxic contraction(0.06±0.03 mN/mm; n=5). Conversely, contractions to ET-1 (10 nM; 0.63±0.09 mN/mm; n=10), a TxA₂ analog (ONO-11113, 100 nM; 0.54±0.05 mN/mm; n=16) and excess K⁺ (0.42±0.15 mN/mm; n=4) were reduced only by about 40-50% compared to term. Acetylcholine (100 mM) and particularly bradykinin (0.1 μM) were less effective in relaxing preterm than term ONO-11113-contracted arteries (46±7% and 27±4% reversal tension, n=5 for both). Regardless of age, tension was nearly completely reversed by sodium nitroprusside (10 μM). We conclude that premature arteries have viable effector mechanisms for contraction and relaxation. However, their capability to generate active agents in response to changes in oxygenation is markedly curtailed, hence explaining the poor postnatal adjustment of the premature. (Supported by HSFO and DFG)