Activation of 5-hydroxytryptamine type 3 receptor-expressing C-fiber vagal afferents inhibits retrotrapezoid nucleus chemoreceptors in rats.

Retrotrapezoid nucleus (RTN) chemoreceptors are regulated by inputs from the carotid bodies (CB) and from pulmonary mechanoreceptors. Here we tested whether RTN neurons are influenced by 5-hydroxytryptamine type 3 receptor-expressing C-fiber vagal afferents. In urethan-anesthetized rats, selective activation of vagal C-fiber afferents by phenylbiguanide (PBG) eliminated the phrenic nerve discharge (PND) and inhibited RTN neurons (n = 24). PBG had no inhibitory effect in vagotomized rats. Muscimol injection into the solitary tract nucleus, commissural part, reduced inhibition of PND and RTN by PBG (73%), blocked activation of PND and RTN by CB stimulation (cyanide) but had no effect on inhibition of PND and RTN by lung inflation. Bilateral injections of muscimol into interstitial solitary tract nucleus (NTS) reduced the inhibition of PND and RTN by PBG (53%), blocked the inhibitory effects of lung inflation but did not change the activation of PND and RTN neurons by CB stimulation. PBG and lung inflation activated postinspiratory neurons located within the rostral ventral respiratory group (rVRG) and inhibited inspiratory and expiratory neurons. Bilateral injections of muscimol into rVRG eliminated PND and partially decreased RTN neuron inhibition by PBG (32%). In conclusion, activation of cardiopulmonary C-fiber afferents inhibits the activity of RTN chemoreceptors. The pathway relays within a broad medial region of the NTS and involves the rVRG to a limited degree. The apnea triggered by activation of cardiopulmonary C-fiber afferents may be due in part to a reduction of the activity of RTN chemoreceptors.