Apnoeic response to stimulation of peripheral GABA receptors in rats.

Respiratory effects of intracarotid injection of gamma-amino-butyric acid (GABA) were investigated in two groups of rats. In the first group of 12 rats the effects of GABA were checked in the intact state, following bilateral vagotomy and GABA receptor blockade. The second group consisted of five initially vagotomized rats, challenged with GABA prior to and after bilateral carotid chemodenervation (CSN-cut). All rats were urethane and chloralose anaesthetized and spontaneously breathing. Injection of 39 micromol/kg GABA prior to and after vagotomy induced an expiratory apnoea of, respectively 5.5+/-0.84 sec and 3.9+/-0.6 sec duration (mean+/-S.E.M.), P>0.05 in all 12 rats. In breaths that followed the apnoea tidal volume increased above the control level by 23.3% (P<0.01) and 25.6% (P<0.01) pre- and post-vagotomy, respectively. Blockade of GABA receptors with bicuculline and picrotoxin abolished the inhibition of breathing. In five vagotomized rats with intact carotid sinus nerves (CSNs) intracarotid GABA challenge increased tidal volume by 39% compared with baseline breathing (P<0.05). Section of the CSNs precluded the occurrence of apnoea and undergoing respiratory changes evoked by GABA. Intracarotid GABA caused significant decrease in the mean blood pressure independent of the neural state, but the fall was delayed by CSNs neurotomy. Results of this study indicate that GABA given systemically induces apnoea followed by post-apnoeic hyperventilation. Carotid bodies are required for the ventilatory response to GABA; vagal afferents are not involved in this response.