Acetylcholine increases pulmonary blood flow in intact fetuses via endothelium-dependent vasodilation

In vitro, acetylcholine causes vasodilation by releasing endothelium- derived relaxing factor (EDRF) from endothelial cells. EDRF may be nitric oxide, derived from the amino acid L-arginine (L-Arg), by a process that is inhibited by N(G)-monomethyl-L-arginine (L-NMMA) and restored by L-Arg. We studied the effect of L-NMMA and L-Arg on the increase in pulmonary blood flow caused by acetylcholine in unanesthetized, intrauterine near-term fetal lambs. Three protocols were employed. In each protocol, acetylcholine (0.48 ± 0.15 μg/kg) was injected at 15-min intervals for 120 min. In the control protocol, nothing else was given. In the second protocol, L-NMMA (14 ± 5 mg/kg) was given at 35 min. In the third protocol, L-NMMA was given at 35 min followed by L-Arg (138 ± 73 mg/kg) at 80 min. In the control protocol, acetylcholine increased pulmonary blood flow 179 ± 17% while it decreased pulmonary arterial pressure 15 ± 1% and did not affect left atrial pressure. The response to each injection lasted <1 min and did not change throughout the experiment. L-NMMA completely blocked, whereas L-Arg completely restored, the effect of acetylcholine on pulmonary blood flow. We conclude that acetylcholine increases pulmonary blood flow in the fetal lamb via the release of EDRF derived from L-Arg. We speculate that endothelium-dependent vasodilation may play a role in the increase in pulmonary blood flow at birth.