Adenosine triphosphate and adenosine increase the pulmonary blood flow to postnatal levels in fetal lambs

ABSTRACT: We investigated the hypothesis that purine nucleotides may mediate the pulmonary vasodilation that occurs at bulb in fetal lambs. We studied nine fetal lambs 3 d after placement of intravascular catheters, a flow transducer around the left pulmonary artery, and an inflatable vascular occluder around the ductus arteriosus. The pressure-flow relationship of left lung during a brief occlusion of the ductus arteriosus was studied as an index of pulmonary vascular resistance. We investigated the pulmonary vascular effects of adenosine, ATP, or saline (control) in doses of 0.01–2.50 μmol/kg/min infused into the right atrial line, and measured blood adenosine and ATP levels in samples from the pulmonary artery and left atrium. We also investigated the mechanism of pulmonary vascular effects of adenosine and ATP. Adenosine and ATP caused significant decreases in pulmonary vascular resistance and increases in pulmonary blood flow in doses of 0.08–2.5 μmol/kg/min. The pulmonary blood flow increased to levels seen in postnatal lambs at doses of 1.2 and 2.5 μmol/kg/min of adenosine and ATP. The baseline blood adenosine and ATP levels in fetus were 8 and 70% of levels in postnatal lambs. ATP concentrations increased to postnatal levels and adenosine levels increased to 20% of postnatal levels at infusion rates of 1.2 and 23 μmol/ kg/rain. The pulmonary vasodilation caused by adenosine and ATP was attenuated by 8-phenyltheophylline and ci-bacron blue, respectively, but not by indomethacin. We conclude that adenosine and ATP are pulmonary vasodilators and increase the fetal pulmonary flow to postnatal levels in doses that increase their blood concentrations to ≤ postnatal levels. The effects of adenosine and ATP are mediated by stimulation of P1 and P2 pnrinergk receptors and are independent of prostacyclin synthesis. Purine nucleotides may be important mediators of pulmonary vasodilation that occurs in the perinatal Iamb.