Benzodiazepines acting on ventral surface of medulla cause airway dilation

The benzodiazepines that have anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic properties affect respiration possibly by acting on gamma-aminobutyric acid (GABA)ergic receptors. This study investigated the effects of benzodiazepines diazepam and midazolam) applied topically to or microinjected just beneath the ventrolateral medullary surface (VMS) on airway tone in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Trachealis smooth muscle tension was assessed by measuring the changes in pressure in a balloon placed in a bypassed rostral segment of the trachea. In 21 cats ventilated with 7% CO2 in O2, surface application of benzodiazepines caused a significant decrease in tracheal tone. Similar to topical application, microinjection of midazolam (1 microgram) in the ventral medulla (0.1-0.2 mm from the surface) in six cats decreased tracheal pressure by 13.2 +/- 2.1 cmH2O (P less than 0.01). In addition, application of benzodiazepines on the VMS in animals ventilated with 12% O2 in N2 (n = 5) decreased tracheal pressure from 15.9 +/- 2.2 to 5.2 +/- 2.7 cmH2O (P less than 0.05). Furthermore, in all cats studied (n = 6), the magnitude of lung deflation-induced tracheal contraction was reduced after application of benzodiazepines on the ventral surface of the medulla (from 11.4 +/- 1.6 to 2.2 +/- 0.9 cmH2O; P less than 0.01). The effects of benzodiazepines on tracheal tone were reversed and blocked by application of Ro 15-1788, a specific benzodiazepines antagonist. However, when parasympathetic activity was abolished by atropine and tracheal tone was restored with 5-hydroxytryptamine, benzodiazepines applied on the VMS had no effect on tracheal pressure. These results suggest that benzodiazepines acting centrally, on structures located near the VMS, can cause a decrease in airway smooth muscle tone by diminishing the activity of parasympathetic neurons which project to the airways.