Tracheal and phrenic responses to neurotensin applied to ventral medulla

Respiratory activity and airway tone can be significantly affected by perturbations confined to superficial areas of the ventrolateral surface of the medulla (VMS). It is not clear which neuromediators are responsible for these changes. Neurotensin (NT), a tridecapeptide, fulfills many of the criteria required for a neurotransmitter or a neuromodulator. In this study, we determined whether NT applied topically to the intermediocaudal area of VMS could alter tracheal tone (Ptseg) and phrenic nerve activity (Ph) in alpha-chloralose-anesthetized cats hyperventilated with O2 to neural apnea. Also, the effects of NT on the responses of tracheal tone and phrenic nerve activity to steady-state hyperoxic hypercapnia (3% CO2 in O2) and isocapnic hypoxia (12% O2) were tested. Application of pledgets containing NT (10(-5)-10(-3) M) caused significant increases in Ptseg and Ph activity without significant changes in blood pressure. Both tracheal and phrenic responses to hypercapnia and hypoxia were also increased by an earlier application of NT. Application of lidocaine (2%) to the VMS rapidly reversed NT-induced responses and prevented them on reapplication of NT. Phosphoramidon, a neutral endopeptidase inhibitor, potentiated responses to NT, suggesting that a mechanism exists at the VMS that could reverse NT effects. Earlier topical administration of hexamethonium bromide to the VMS did not influence the effects of NT, indicating that NT was not acting by causing the release of acetylcholine. Intravenous administration of atropine (1 mg/kg) blocked tracheal but not phrenic responses to NT. These findings suggest that neurotensin may be a neuromodulator involved in central chemosensitivity and that it may participate in the regulation of phrenic activity and parasympathetic tone of airway smooth muscle.