To determine the effects of birth-related stimuli on L-arginine-dependent vasodilation or nitric oxide (NO) activity in the perinatal lung, we studied the fetal pulmonary vascular effects of nitro-L-arginine (L-NA), a specific inhibitor of NO formation, during 1) mechanical ventilation without altering fetal blood gas tensions; 2) administration of high oxygen concentrations; and 3) increased flow or shear stress. In the first protocol, 13 late-gestation fetal lambs were ventilated with low fraction of inspired oxygen concentration (FI(O2) less-than-or-equal-to 0.10) for 60 min after infusion of L-NA or saline into the left pulmonary artery (LPA). In control animals, LPA flow steadily increased during 60 min of ventilation. With L-NA treatment, the rise in flow and decrease in total pulmonary resistance (TPR) were reduced 67% (P < 0.001 vs. control) and 28% (P < 0.01 vs. control), respectively. Subsequent ventilation with high FI(O2) (1.00) decreased mean pulmonary arterial pressure (PAP) in control but not in L-NA-treated animals. TPR remained fourfold greater in L-NA-treated animals than in control animals (P < 0.001). In the second protocol, with partial compression of the ductus arteriosus, LPA flow increased 300% and TPR decreased 61% over 30 min. After L-NA treatment the rise in blood flow and decrease in TPR was markedly attenuated (P < 0.001). We conclude that the perinatal pulmonary vasodilator response to ventilation without changing arterial oxygen tension and ventilation with increased oxygen tension are modulated by NO. In addition, flow or shear stress-induced vasodilation is mediated by NO release. We speculate that stimulation of NO formation during ventilation may be augmented by increased shear stress during the transition.
