Abstract

Orexin modulates CO2‐drive to breath and there is an extensive population of orexin receptor 1 (OX1R) in the Locus coeruleus (LC). We tested the hypothesis that OX1R located in the LC is involved in chemoreception. To this end, we injected SB‐334867 (OX1R antagonist, 5 mM) into the LC of male Wistar rats. Pulmonary ventilation (VE), body temperature (Tb, dataloggers), mean arterial pressure (MAP) and heart rate (HR) were measured in air followed by hypercapnia (7% CO2) in unanesthetized rats. Hypercapnia caused an increase in VE, which resulted from increases in respiratory frequency (fR) and tidal volume (VT), but did not affect MAP, fH or Tb in all groups. SB‐334867 caused a significant attenuation (70%), of the hyperpnea induced by hypercapnia (n=9) compared with its vehicle (n=6; P< 0.05). This effect was due to both decreased VT and f. Basal ventilation, MAP, HR or Tb, were not affected by OX1R antagonism. These results suggest that projections of orexin‐containing neurons to the LC contribute via orexin R1 to the hypercapnic chemoreflex control in unanesthetized rats.Grant Funding Source: FAPESP and CNPq

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