Type I (neuronal) nitric oxide synthase (NOS) has been detected in fetal rat lung, but its functional role in the developing lung is unknown. To study the potential contribution of Type I NOS in regulation of basal fetal pulmonary vascular resistance (PVR), and to determine whether it is present in the ovine fetal lung, we measured the hemodynamic effects of a selective Type I NOS antagonist, 7-nitroindazole (7-NINA) and a non-selective NOS antagonist, nitro-L-arginine (L-NA), in 4 chronically prepared fetal lambs (mean age 128± 2 days; term, 147 days). At surgery, catheters were placed in the left pulmonary artery (LPA) for selective drug infusion, and in the main pulmonary artery (PAP), aorta (Ao), left atrium (LAP), and amniotic cavity for pressure measurements. An ultrasonic flow transducer was placed on the the LPA to measure blood flow (Q). PVR in the left lung was calculated as PAP-LAP/Q. After at least 72 hours of recovery from surgery, 7-NINA (2 mg) and L-NA (20 mg) were infused in random order into the LPA over 10 minutes on seperate days. 7-NINA increased basal PVR in the left lung, as was observed after treatment with L-NA. This increase in PVR persisted for up to 60 minutes after the infusion of 7-NINA. p Value = comparison of baseline vs treatment. Table

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Acetylcholine-induced pulmonary vasodilation remained intact after treatment with 7-NINA, but was inhibited after L-NA, suggesting minimal effects of on Type III (endothelial) NOS after 7-NINA infusion. Western blot analysis detected Type I NOS in the 70 day, 90 day, 125 day, and 140 day fetal lung, as well as in the day 1 newborn lung. The pattern suggests a peak of Type I NOS expression at 125 days, with a decrease towards term. We conclude that a selective Type I NOS antagonist increases basal PVR in the late-gestation fetus, and that Type I NOS protein is present in the ovine fetal lung. We speculate that Type I NOS may modulate vascular tone in the developing pulmonary circulation.