PURINE NUCLEOTIDES CONTRIBUTE TO PULMONARY VASODILATION CAUSED BY BIRTH-RELATED STIMULI IN THE OVINE FETUS

We investigated the hypothesis that the purine nucleotides ATP and ade nosine mediate the pulmonary vasodilation that occurs at birth in feta l lambs. We instrumented 44 fetal lambs to measure left pulmonary arte rial pressure and flow. In control studies, we investigated the effect s of sequential ventilation with 10, 50, and 100% O-2 on fetal pulmona ry arterial pressure and flow and pulmonary vascular resistance (PVR). We also measured the blood and plasma ATP levels in the pulmonary art ery and left atrium in the control studies. In three separate groups o f studies, we investigated the effects of 8-phenyltheophylline, an ade nosine-receptor antagonist, and cibacron blue, an inhibitor of ATP-sen sitive P-2y receptors, given alone or in combination, on the response of PVR to sequential ventilation. Fetal arterial PO2 increased during ventilation with 50 and 100% O-2 but not with 10% O-2. Ventilation wit h 10% O-2 caused a 4-fold increase in pulmonary blood flow and a 10-fo ld decrease in PVR. Ventilation with 50 and 100% O-2 caused a 7-fold i ncrease in pulmonary blood flow and a 20-fold decrease in PVR. Blood a nd plasma ATP levels in the pulmonary artery and blood ATP levels in t he left atrium increased significantly during ventilation with 50 and 100% O-2 but not with 10% O-2. Pretreatment of animals with 8-phenylth eophylline attenuated the increase in pulmonary flow and decrease in P VR caused by ventilation at all fractions of inspired O-2 (FIO2 levels ). Pretreatment of animals with cibacron blue attenuated pulmonary vas odilation at 50 and 100% FIO2. Combined treatment with 8-phenyltheophy lline and cibacron blue caused complete inhibition of the decrease in PVR in response to ventilation at the three FIO2 levels. Incubation of fetal red blood cells in vitro with 100% O-2 caused an increase in AT P production. An increase in arterial PO2 in the fetus causes an incre ase in blood ATP levels, and an inhibition of ATP receptors attenuates the O-2-induced decrease in PVR. Adenosine-receptor inhibition attenu ates both ventilation- and O-2-induced changes in PVR. Increased synth esis and release of ATP plays a major role in causing pulmonary vasodi lation in response to birth-related stimuli in the ovine fetus.