Adenosine A(2A) receptors mediate hypoxic inhibition of fetal breathing in sheep.
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 A(1) and/or A(2A)receptor subtypes mediate the depressant effects of hypoxia.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Hypoxic inhibition of rapid eye movements and breathing is critically dependent on activation of adenosine A(2A) receptors.
Koos
Brian J
BJ
Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Brain Research Institute, University of California, Los Angeles School of Medicine, 90095-1740, USA..
Maeda
Takatsugu
T
Jan
Calvin
C
Lopez
Grace
G
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004569:Electroencephalography; D004585:Electrooculography; D005133:Eye Movements; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005324:Fetal Movement; D005333:Fetus / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood; D011247:Pregnancy; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012119:Respiration; D012756:Sheep; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D002245:Carbon Dioxide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D010100:Oxygen