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Adenosine A2A receptors mediate hypoxic inhibition of fetal breathing in sheep

  • Brian J. Koos
    Affiliations
    Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Brain Research Institute, University of California, Los Angeles School of Medicine. Los Angeles, Calif
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  • Takatsugu Maeda
    Affiliations
    Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Brain Research Institute, University of California, Los Angeles School of Medicine. Los Angeles, Calif
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  • Calvin Jan
    Affiliations
    Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Brain Research Institute, University of California, Los Angeles School of Medicine. Los Angeles, Calif
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  • Grace Lopez
    Affiliations
    Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Brain Research Institute, University of California, Los Angeles School of Medicine. Los Angeles, Calif
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      Abstract

      Objective: Hypoxia inhibits fetal breathing through activation of central adenosine (ADO) receptors that modulate fetal behavioral state. This study was designed to determine whether adenosine A1 and/or A2Areceptor subtypes mediate the depressant effects of hypoxia. Study design: In 14 chronically catheterized fetal sheep (>0.8 term), hypoxemia was induced by having the ewe breathe a gas mixture of 9% oxygen for 1 hour. During hypoxia, the fetus was infused intra-arterially with a vehicle or an antagonist for adenosine A1 or A2A receptors. Statistical analysis was performed by using analysis of variance with Tukey's least significant difference criterion. Results: Fetal isocapnic hypoxemia (PaO2: control, ~24 mm Hg; hypoxia, ~14 mm Hg) virtually eliminated rapid eye movements and breathing when the fetus was infused with vehicle or the A1 receptor antagonist. In contrast, adenosine A2A receptor blockade abolished the hypoxia-induced arrest of rapid eye movements and breathing. Conclusion: Hypoxic inhibition of rapid eye movements and breathing is critically dependent on activation of adenosine A2A receptors. (Am J Obstet Gynecol 2002;186:663-8.)

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