ABSTRACT
AIM: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid µ-receptors have been found in the MR, we studied the putative role of opioid µ-receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. METHODS: We measured pulmonary ventilation (VE) and the body temperatures (Tb) 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 per 0.1 µL) was microinjected into the rMR during normoxia or after 60 min of hypoxia. RESULTS: The animals treated with intra-rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg(-1) min(-1)) compared with the control group (790 ± 82 mL kg(-1) min(-1) ) (P < 0.05). No differences in the Tb were observed between groups during hypoxia. CONCLUSION: These data suggest that opioids acting on µ-receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.
Subject(s)
Hyperventilation/etiology , Hypoxia/complications , Pulmonary Ventilation , Raphe Nuclei/metabolism , Receptors, Opioid, mu/metabolism , Respiratory Mechanics , Animals , Body Temperature , Consciousness , Disease Models, Animal , Hyperventilation/metabolism , Hyperventilation/physiopathology , Hypoxia/metabolism , Hypoxia/physiopathology , Male , Microinjections , Narcotic Antagonists/administration & dosage , Peptide Fragments/administration & dosage , Pulmonary Ventilation/drug effects , Raphe Nuclei/drug effects , Raphe Nuclei/physiopathology , Rats , Rats, Wistar , Receptors, Opioid, mu/antagonists & inhibitors , Respiratory Mechanics/drug effects , Somatostatin/administration & dosage , Time FactorsABSTRACT
AIM: In the present study, we assessed the role of 5-hydroxytryptamine (5-HT) receptors (5-HT(1A), 5-HT(2) and 5-HT(7)) in the nucleus raphe magnus (NRM) on the ventilatory and thermoregulatory responses to hypoxia. METHODS: To this end, pulmonary ventilation (V(E)) and body temperature (T(b)) of male Wistar rats were measured in conscious rats, before and after a 0.1 microL microinjection of WAY-100635 (5-HT(1A) receptor antagonist, 3 microg 0.1 microL(-1), 56 mm), ketanserin (5-HT(2) receptor antagonist, 2 microg 0.1 microL(-1), 36 mm) and SB269970 (5-HT(7) receptor antagonist, 4 microg 0.1 microL(-1), 103 mm) into the NRM, followed by 60 min of severe hypoxia exposure (7% O(2)). RESULTS: Intra-NMR microinjection of vehicle (control rats) or 5-HT antagonists did not affect V(E) or T(b) during normoxic conditions. Exposure of rats to 7% O(2) evoked a typical hypoxia-induced anapyrexia after vehicle microinjections, which was not affected by microinjection of WAY-100635, SB269970 or ketanserin. The hypoxia-induced hyperpnoea was not affected by SB269970 and ketanserin intra-NMR. However, the treatment with WAY-100635 intra-NRM attenuated the hypoxia-induced hyperpnoea. CONCLUSION: These data suggest that 5-HT acting on 5-HT(1A) receptors in the NRM increases the hypoxic ventilatory response.
