Resistive loading reduces ventilatory response to strychnine in anesthetized rabbits

Breathing through an inspiratory resistance induces a hypoventilation in mammals despite an increased diaphragmatic activity. We showed in previous works that an increase in GABA and endogenous opioid release in the central respiratory network could explain in part the inadequate increase in the inspiratory drive during inspiratory loading. In the present experiment, we speculated about an additional role of glycine, another inhibitory neurotransmitter. The ventilatory effects of the glycine antagonist strychnine were evaluated in two groups of anesthetized rabbits, breathing either through an inspiratory resistive load (IRL) or not (control group). In the control group, strychnine raised (+7%, P < 0.05) the minute ventilation, V, and the rate of increase in integrated diaphragmatic discharge (Edi peak/T peak: +29%, P < 0.01). In the IRL group, strychnine did not change V and produced a lesser increase in Edi peak/T peak (+9%, P < 0.05). In both groups, strychnine induced a tonic diaphragmatic discharge. These data show that there is a weak inhibition of inspiration by glycine during resistive loading, but the effect is modest compared with that observed during unloaded ventilation. Thus, it seems that IRL breathing reduces the efficacy and/or the release of this neurotransmitter in the central nervous system, in this experimental situation.