Premium
Antagonism of orexin receptor 1 (OX 1 R) in the retrotrapezoid nucleus (RTN) inhibits the ventilatory response to hypercapnia in wakefulness.
Author(s) -
Dias Mirela Barros,
Li Aihua,
Nattie Eugene E
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.621.12
Subject(s) - wakefulness , hypercapnia , ventilation (architecture) , hyperventilation , control of respiration , orexin , chemoreceptor , anesthesia , endocrinology , medicine , microinjection , chemistry , respiratory system , neuroscience , receptor , biology , neuropeptide , electroencephalography , mechanical engineering , engineering
Recent transgenic mice data suggest that OX plays an important role in CO 2 sensitivity during wake periods. We hypothesized that OX 1 R in the RTN contribute to chemoreception. In unanesthetized rats, ventilation was recorded using a whole body plethysmograph, together with EEG and EMG. We dialyzed the vehicle and then SB‐334867 (OX 1 R antagonist) into the RTN to focally inhibit OX 1 R and studied the effects of both treatments on breathing in air and in 7%CO 2 . During wakefulness, but not during sleep, SB‐334867 caused a 26% reduction of the hyperventilation induced by 7%CO 2 (135 ± 10 mL/100g/min) compared with vehicle (182 ± 10 mL/100g/min) (P< 0.01). This effect was due to both decreased Vt and f . Neither basal ventilation nor oxygen consumption was affected. The number and duration of apneas were similar between control and treatment periods. No effect was observed in a separate group of animals who had the microdialysis probe misplaced (peri‐RTN). Acute exposure to 7%CO 2 tends to awaken or arouse rats and did so in the peri‐RTN group. Compared to the peri‐RTN group, treatment with SB‐334867 in the RTN decreased the awake period during 7%CO 2 (P<0.05). We conclude that projections of orexin‐containing neurons to the RTN contribute via OX 1 R to the hypercapnic chemoreflex control during wakefulness, but not during the sleep. Further, RTN OX 1 R may be a part of the circuit that modulates the arousal response to hypercapnia. (HL 28066)