A Potential Role for Adenosine in the Inhibition of Nonshivering Thermogenesis in the Fetal Sheep

Adenosine is released by the placenta into the fetal circulation and has potent antilipolytic properties in vitro. Nonshivering thermogenesis cannot be demonstrated by cooling fetal sheep in utero but can be induced by supplemental oxygenation and umbilical cord occlusion; this suggests the presence of inhibitor(~) of placental origin. To test whether circulating adenosine could be such an inhibitor, a series of experiments was carried out in nine fetal sheep at 136-145 d gestation. Birth was simulated in utero by sequentially cooling the fetus 2.49 ? 0.23"C with no change in the low levels of plasma FFA or glycerol; ventilating with 0, via an exteriorized tracheostomy tube and umbilical cord occlusion. Thermogenic indices rose markedly, and plasma FFA and glycerol concentrations peaked at 725 + 88 pEq/L (p < 0.01) and 771 -C 154 pmoVL, (p < 0.001), respectively, 0, consumption rose to 20 + 2 mUminkg, and temperature increased 1.99 ? 0.35"C. The long-acting adenosine analog N6-(L-2-phenylisopropy1)-adenosine (PIA) was