Microinjection of kynurenic acid and lidocaine into the dorsal motor nucleus of vagus evokes airway smooth muscle relaxation in ferrets.

The dorsal motor nucleus of vagus (DMV) provides a critical source of parasympathetic motor output to the airway smooth muscle; however, the central neurotransmitter mechanisms that regulate this activity remain incompletely understood. This study investigated how blockade of excitatory glutamatergic transmission or transient functional suppression of the DMV modulates vagally mediated airway constriction in anaesthetized ferrets (n = 10), divided into two experimental groups (n = 5 per group). Animals were maintained under alpha-chlorose anesthesia and mechanically ventilated. The pressure in the tracheal segment (Ptseg), lung resistance (RL), and dynamic compliance (Cdyn) were continuously recorded. Physostigmine (40 µg/kg) evoked a robust increase in Ptseg (8.6 ± 0.52 → 24.1 ± 2.86 cm H₂O, p < 0.001) and RL (0.097 ± 0.022 → 0.309 ± 0.051 cm H₂O·s·L⁻¹, p < 0.001), with a concomitant decrease in Cdyn (0.886 ± 0.050 → 0.464 ± 0.043 L·cm H₂O⁻¹, p < 0.001). Bilateral microinjection of kynurenic acid (10 nmol) into the DMV reduced Ptseg to 11.12 ± 1.95 cm H₂O (p < 0.01 vs Physostigmine), decreased RL to 0.132 ± 0.016 cm H₂O·s·L⁻¹ , and increased Cdyn to 0.692 ± 0.062 L·cm H₂O⁻¹ . Lidocaine (2%) microinjection elicited comparable effects (Ptseg: 28.3 ± 3.67 → 9.96 ± 1.76 cm H₂O; p < 0.01). These interventions reversed cholinergic bronchoconstriction and restored pulmonary compliance to baseline. Collectively, these findings demonstrate that excitatory glutamatergic transmission within the DMV sustains vagal parasympathetic outflow to the airways, and that its inhibition, either by receptor blockade or neuronal silencing, produces central bronchodilation.