Opioid μ‐receptors in the rostral medullary raphe modulate hypoxia‐induced hyperpnea in unanesthetized rats

Abstract

It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As the rostral MR (rMR) expresses an extensive population of opioid μ‐receptors, we studied the putative role of opioid μ‐receptors in the rMR region on ventilation in normal and 7% hypoxic conditions. We measured pulmonary ventilation and the body temperatures of male Wistar rats before and after the selective opioid μ‐receptor antagonist CTAP (D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2, cyclic, 0.1 μg/0.1 μL) was microinjected into the rMR during normoxia or after 60 minutes of hypoxia. The animals treated with intra‐rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg−1 min−1) compared to the control group (790 ± 82 mL kg−1 min−1) (P<0.05) due to a reduced tidal volume (3.0 ± 0.41 versus 6.1 ± 0.6 ml kg−1; P<0.05). During hypoxic recovery, the ventilation remained reduced in the CTAP intra‐rRM group. No differences in the Tb were observed among groups during hypoxia. These data suggest that opioids acting on μ‐receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.Financial support: FAPESP, CNPq, PRONEX.