GAMMA-AMINOBUTYRIC-ACID CONTRIBUTES TO MODULATION OF CARDIORESPIRATORY CONTROL AFTER CHRONIC VENTILATORY LOADING

Diseases imposing chronic ventilatory loads may depress ventilation an d cause chronic hypercapnia. This may be a result of mechanical loadin g imposed on pre-existing decreased respiratory drive or functional al teration of neural circuits involved in ventilatory control. To evalua te these possibilities, chronic resistive airway loading was imposed i n rats via a circumferential tracheal band which tripled tracheal resi stance (obstructed group). Sham surgery was performed in controls. Aft er 8 weeks, animals were anesthetized (urethane) and tracheostomy perf ormed relieving increased tracheal resistance. The ventral medullary s urface (VMS) was exposed and the intermediate area (IA) identified. Th e integrated diaphragm EMG (EMG(DI)) was recorded. The obstructed grou p was hypercapnic while controls were eucapnic (P-CO2, 45.1 +/- 719 vs . 37.6 +/- 3.4 Torr; P < 0.001). Respiratory rate (RR) remained lower in obstructed than in control animals despite relief of the resistive load by tracheostomy (58.5 +/- 5.1 vs. 75.4 +/- 5.4 bpm; P < 0.05). Ap plication of 1 mM bicuculline soaked pledgets (BIC) to the IA of the V MS significantly increased EMG(DI) in obstructed but not in control an imals (27.5 +/- 5.5 vs. 5.2 +/- 4.4%; P < 0.006). RR was unaffected. M ean arterial pressure increased with BIC in obstructed but not control animals (23.0 +/- 6.5 vs. 4.5 +/- 3.5%; P < 0.02). These data suggest that alteration of cardiorespiratory control occurs during chronic re sistive hypercapnic loading and that GABAergic neurons in the VMS part icipate in this adaptive response. (C) 1997 Elsevier Science B.V.