Changes in dopamine D(2)-receptor modulation of the hypoxic ventilatory response with chronic hypoxia.
Modulation of the hypoxic ventilatory response (HVR) by dopamine D(2)-receptors (D(2)-R) in the carotid body (CB) and central nervous system (CNS) are hypothesized to contribute to ventilatory acclimatization to hypoxia. We tested this with blockade of D(2)-R in the CB or CNS in conscious rats after 0, 2 and 8 days of hypoxia. On day 0, CB D(2)-R blockade significantly increased VI and frequency (fR) in hyperoxia (FI(O(2))=0.30), but not hypoxia (FI(O(2))=0.10). CNS D(2)-R blockade significantly decreased fR in hypoxia only. On day 2, neither CB nor CNS D(2)-R blockade affected VI or fR. On day 8, CB D(2)-R blockade significantly increased hypoxic VI and fR. CNS D(2)-R blockade significantly decreased hypoxic VI and fR. CB and CNS D(2)-R modulation of the HVR decreased after 2 days of hypoxia, but reappeared after 8 days. Changes in the opposing effects of CB and CNS D(2)-R on the HVR during chronic hypoxia cannot completely explain ventilatory acclimatization in rats.
Huey
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Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0623, USA. khuey@uci.edu
Brown
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Jordan
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Powell
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D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004294:Domperidone / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D002245:Carbon Dioxide; D004294:Domperidone; D006220:Haloperidol; D010100:Oxygen