GABA(B) receptor blockade reduces resistive loading-induced hypoventilation in anesthetized rabbits

We hypothesized that hypoventilation induced by resistive loaded breathing may result in part from the inhibition of central respiratory-related structures by gamma-aminobutyric acid (GABA), through the stimulation of GABA(B) receptors. In that case, ventilatory depression should be minimized by GABA(B) receptor blockade. To test this assumption, the ventilatory effects of a GABA(B) receptor antagonist (CGP 35348) were evaluated in two groups of urethane anesthetized rabbits, breathing either through an inspiratory resistive load (IRL group) or not (Control group). CGP 35348 did not modify baseline ventilation in the Control group. On the other hand, it partially reversed IRL-induced hypoventilation through a higher respiratory rate and central inspiratory drive. These data suggest that, unlike GABA(A) receptors, GABA(B) receptors would not play a part in eupneic breathing, but that they could participate in the hypoventilation resulting from an acute increase in the work of breathing.