Type II (inducible) nitric oxide synthase (NOS II) is present in the fetal lung and modulates basal pulmonary vascular tone in the late gestation fetal lamb. To determine whether NOS II contributes to nitric oxide (NO) activity in response to shear stress-induced pulmonary vasodilation, we studied the response of two selective NOS II antagonists, aminoguanidine (AG) and S-ethylisothiourea (EIT), and a non selective NOS antagonist, nitro-L-arginine(L-NA), on pulmonary vascular resistance (PVR) during acute partial compression of the ductus arteriosus (DA) in 10 chronically prepared fetal lambs (mean age 132 ± 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 LPA to measure blood flow (Q). PVR in the left lung was calculated as PAP-LAP/Q. An inflatable occluder was placed around the DA for compression. After at least 72 hours of recovery from surgery, normal saline(control), AG (120 mg), EIT (0.12 mg), and L-NA (20 mg) were infused in random order into the LPA over 10 minutes. On alternate days, the DA was compressed to increase PAP 12-15 mmHg above baseline values for 30 minutes. In comparison with the 50% reduction in PVR in controls, AG and EIT reduced the fall in PVR, and L-NA paradoxically increased PVR. Table

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We conclude that selective Type II (inducible) nitric oxide synthase antagonists attenuate shear stress-induced pulmonary vasodilation in the late gestation fetus. We speculate that Type II nitric oxide synthase may contribute to NO formation during shear stress-induced pulmonary vasodilation.