To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)