Neural mechanism of glottal closure evoked by anandamide in the rat

Abstract

Capsaicin-induced activation of pulmonary vagal C-fiber (PCF) receptors evokes glottal closure via excitation to the adducent branch and inhibition on the abducent branch of the recurrent laryngeal nerve (Add RLN and Abd RLN, respectively). We attempted to investigate whether anandamide, an endogenous agonist of TRPV1 and cannabinoid receptor, could also evoke a similarly reflexive effect on the glottis and RLN. We first observed a tight glottal closure in the spontaneously breathing rat during intra-jugular administration of anandamide. We then recorded the activity of the phrenic nerve, Add RLN and Abd RLN simultaneously in the anesthetized and ventilated rats. Our results showed that anandamide administration evoked an enhancement of Add RLN during the period of apnea and recovery from apnea. This enhancement of Add RLN activity was reflected on an earlier onset during inspiration and increase in Add RLN activity in combination with a delay onset and decrease of Abd RLN discharge. These laryngeal reflexes were abolished after blockade of PCF conduction by perineural capsaicin treatment on the bilateral cervical vagi and by pretreatment with capsazepine (a TRPV1 antagonist) but not with AM 281 (a selective cannabinoid receptor 1 antagonist). These results suggest that anandamide-induced glottal closure is mediated through activation of TRPV1 on the PCF to produce a reflex modulation of the RLN activity.