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(s) 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 degrees C with no change in the low levels of plasma FFA or glycerol; ventilating with O2 via an exteriorized tracheostomy tube and umbilical cord occlusion. Thermogenic indices rose markedly, and plasma FFA and glycerol concentrations peaked at 725 +/- 88 microEq/L (p < 0.01) and 771 +/- 154 mumol/L, (p < 0.001), respectively, O2 consumption rose to 20 +/- 2 mL/min/kg, and temperature increased 1.99 +/- 0.35 degrees C. The long-acting adenosine analog N6-(L-2-phenylisopropyl)-adenosine (PIA) was then infused (90 micrograms/kg bolus, then 300 micrograms/kg/h for 30 min); plasma FFA and glycerol decreased to 265 +/- 56 microEq/L (p < 0.003) and 477 +/- 102 mumol/L (p < 0.04), respectively; O2 consumption fell rapidly to 4.5 +/- 0.3 mL/min/kg (p < 0.01); temperature decreased 1.89 +/- 0.39 degrees C (p < 0.001); and fetal arterial BP decreased to 38 +/- 5 mm Hg (p < 0.004) in 30 min. A stepped dose-response study was performed in three fetal sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Ball
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KT
Department of Paediatrics, School of Medicine, University of Auckland, New Zealand.
Gunn
T R
TR
Power
G G
GG
Asakura
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H
Gluckman
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PD
D000241:Adenosine / Q000097:blood / Q000502:physiology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D012121:Respiration, Artificial; D012756:Sheep
D010660:Phenylisopropyladenosine; D000241:Adenosine; D010100:Oxygen