Endothelium-derived nitric oxide (EDNO) modulates fetal pulmonary vasoactivity. The role of EDNO in regulation of vasomotor tone in fetal pulmonary arteries vs. that in veins is not known. We have investigated the role of EDNO in the responses of pulmonary arteries and veins of full-term fetal lambs. Fourth-generation pulmonary arterial and venous rings were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2 at 37 degrees C), and their isometric force was measured. N omega-nitro-L-arginine had no effect on the resting tension of pulmonary arteries with endothelium but caused contraction of pulmonary veins with endothelium. The basal level of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) of pulmonary veins with endothelium was higher than that of arteries with endothelium. In pulmonary arteries, bradykinin, but not acetylcholine, induced endothelium-dependent relaxation and an increase in cGMP content. In pulmonary veins, acetylcholine, but not bradykinin, induced endothelium-dependent relaxation and an increase in cGMP content. Agonist-induced maximal relaxation and increases in cGMP content were smaller in pulmonary arteries than in veins. All these endothelium-dependent responses were abolished by N omega-nitro-L-arginine. In tissues without endothelium, nitric oxide induced significantly less relaxation and less increase in cGMP content in pulmonary arteries than in pulmonary veins. All vessels relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Our data suggest that the role of EDNO in modulating tone differs between pulmonary arteries and veins in full-term fetal lambs.(ABSTRACT TRUNCATED AT 250 WORDS)