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Airway tone can be modulated centrally by the brain as well as by peripheral receptors. In part these changes in airway caliber seem to be secondary to changes in respiratory activity. Since structures near the ventrolateral medullary surface (VMS) can produce profound effects on respiration, it seems reasonable to believe that they might also be capable of modifying tracheal tone. In this study we examined the effects of two agents with respect to their action on tracheal tone: nicotine, a respiratory stimulant when applied to the VMS, and gamma aminobutyric acid (GABA), a respiratory depressant when similarly administered. In chloralose anesthetized, paralyzed, artificially ventilated cats, tracheal tone was assessed by measuring pressure changes in a rostral bypassed segment of the trachea, while phrenic nerve activity was examined simultaneously. Nicotine administered on the intermediate area of the VMS both before and after carotid sinus denervation increased phrenic activity and induced constriction of the rostral tracheal segment. The response to nicotine could be blocked by application of a nicotine antagonist, hexamethonium, or prior local administration of lidocaine to the VMS. Activation of GABAergic receptors by application of GABA on the intermediate area of the VMS markedly reduced respiratory activity and nearly abolished the increased tracheal tone produced by inhalation of 7% CO2 in O2. The effects of GABA were eliminated by the prior administration to the VMS of bicuculline, a GABA receptor antagonist. These results indicate that structures located on the ventral surface of the medulla which affect breathing may also play a significant role in the regulation of airway smooth muscle tone.

Nasal resistance is known to be affected by changes in nasal blood volume and hence to depend on sympathetic discharge to nasal blood vessels. Structures located superficially near the ventrolateral surface of the medulla significantly affect respiratory and sympathetic activity and the tone of the trachea. To assess the importance of these structures on nasal patency, we measured transnasal pressure at a constant flow and examined the change in pressure produced by topically applied N-methyl-D-aspartic acid (NMDA). Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. NMDA administered on the intermediate area of the ventral surface of the medulla decreased transnasal pressure and increased phrenic nerve activity. The response to NMDA could be diminished or abolished by application to the ventral medullary surface of the NMDA antagonist 2-amino-5-phosphonovalerate (2-APV) or the local anesthetic lidocaine. Carotid sinus denervation and posthypothalamic decerebration did not alter the nasal and phrenic nerve responses to NMDA; however, cervical sympathetic denervation decreased these responses, both in intact and in bilaterally adrenalectomized animals. Therefore, activation of NMDA receptors on structures near the ventral surface of the medulla increases tone in the nasal vasculature and leads to a response pattern that includes changes in not only phrenic nerve activity and blood pressure but also nasal patency.

Respiratory chemical and reflex interventions have been shown to affect nasal resistance or tracheal tone, respectively. In the present study, nasal caliber (assessed from pressure at a constant flow) and tracheal tone (assessed from pressure in a fluid-filled balloon within an isolated tracheal segment) were monitored simultaneously in anesthetized, paralyzed, artificially ventilated (inspired O2 fraction = 100%) cats. We examined the effect of CO2 inhalation and sciatic nerve stimulation as well as the application of nicotine (6 X 10(-4) mol/l) or lidocaine (2% solution) to the intermediate area of the ventral medullary surface (VMS). CO2 and VMS nicotine resulted in a significant increase in tracheal pressure [147 +/- 73 and 91 +/- 86% (SD), respectively]; and a significant reduction in nasal pressure (-35 +/- 10 and -20 +/- 13%, respectively). In contrast, sciatic nerve stimulation resulted in a significant fall in both tracheal (-50 +/- 36%) and nasal pressure (-21 +/- 13%). Application of 2 or 4% lidocaine to the VMS reduced tracheal pressure but did not significantly affect nasal pressure. After VMS lidocaine, nasal and tracheal responses to CO2, sciatic nerve stimulation, or VMS nicotine, when present, were negligible. These results suggest a role for the VMS in the regulation and coordination of nasal and tracheal caliber responses.