Adenosine A(2A) receptors mediate hypoxic inhibition of fetal breathing in sheep.

Abstract

Hypoxia inhibits fetal breathing through activation of central adenosine (ADO) receptors that modulate fetal behavioral state. This study was designed to determine whether adenosine A(1) and/or A(2A)receptor subtypes mediate the depressant effects of hypoxia. 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 A(1) or A(2A) receptors. Statistical analysis was performed by using analysis of variance with Tukey's least significant difference criterion. Fetal isocapnic hypoxemia (PaO(2): control, approximately 24 mm Hg; hypoxia, approximately 14 mm Hg) virtually eliminated rapid eye movements and breathing when the fetus was infused with vehicle or the A(1) receptor antagonist. In contrast, adenosine A(2A) receptor blockade abolished the hypoxia-induced arrest of rapid eye movements and breathing. Hypoxic inhibition of rapid eye movements and breathing is critically dependent on activation of adenosine A(2A) receptors.