Effect of Systemic Application of 5-Hydroxytryptamine on Hypoglossal Nerve Discharge in Anesthetized Rats.

The aim of this study is to investigate whether systemic 5-hydroxytryptamine (5-HT) can promote long-lasting form of respiratory plasticity in vivo via 5-HT2AR-activated protein kinase C (PKC) mechanism. The frequency and peak amplitude of hypoglossal nerve discharges in anesthetized rats were compared before and after intravenous injections of different treatments, including saline, 5-HT, ketanserin tartrate, or staurosporine. The administration of 5-HT at a systemic bolus imposed an initial ephemeral inhibition subsequently followed by striking facilitation, which demonstrates a biphasic manner of hypoglossal nerve output in anesthetized adult rats. The facilitatory stage conformed to the reinforced hypoglossal activity that lasted for more than 60 min after drug administration. The 5-HT evoked biphasic manner of hypoglossal output and hypoglossal nerve activity LTF (hLTF) were 5-HT2A receptor-dependent and coupled to PKC activation. The initial inhibition of hypoglossal activity was associated with nodose ganglion, and the subsequent facilitation was associated with carotid body. The reactive oxygen species (ROS) formation was triggered in the systemic 5-HT2-dependent hLTF model in vivo. The expressions of immunofluorescent histochemistry provide morphological evidence of a 5-HT/5-HT2A receptor coupled to PKC mechanism. In conclusion, systemic 5-HT challenge contributes to long-lasting form of respiratory plasticity and to elicit hLTF or elevated hLTF in animals, which with decreased or even with inhibited peripheral inhibitory activations. The effect of systemic 5-HT was regulated by a 5-HT2AR-activated PKC mechanism.

[The influence of intermittent hypoxia on long-term facilitation of hypoglossal nerve discharge in spontaneously breathing rats].

OBJECTIVE: To explore the impact of intermittent hypoxia on long-term facilitation (LTF) of hypoglossal nerve discharge. METHODS: Twelve adult SD rats were divided into the experimental group (CIH group, n = 6) and the control group (normoxia group, n = 6) by the random number table. The rats in the CIH group were fed in the intermittent hypoxia animal chambers, while the control group was placed in the normoxia animal chambers for 8 h per day (from 8:00 AM to 4:00 PM) for 4 consecutive weeks. After that, 5 min×3 stimulations of acute intermittent hypoxia (AIH) were administered and the hypoglossal never signals were recorded before and after AIH. RESULTS: The baseline frequency and average peak amplitude of hypoglossal nerve discharge in the CIH experimental group were significantly greater than those in the control group. The discharge frequency in the CIH and the control groups was (73 ± 13) Hz, and (58 ± 11) Hz, respectively(P < 0.05); and the discharge amplitude in the 2 groups was (4.6 ± 1.1) µV, and (3.3 ± 0.7) µV, respectively(P < 0.05). After intervention with AIH, the frequency and the average peak amplitude of the hypoglossal nerve discharge in the experimental and the control groups were significantly increased(all P < 0.05). The increased discharge lasted more than 1 h and this typical phenomenon was referred to as LTF. In the CIH group, the discharge frequency before and after exposure to AIH was (68 ± 16) Hz and (133 ± 20) Hz, respectively; and the discharge amplitude was (4.6 ± 1.1) µV and (8.9 ± 1.4) µV, respectively. In the control group, the discharge frequency before and after AIH was (59 ± 12) Hz and (102 ± 16) Hz, respectively; and the discharge amplitude was (3.3 ± 0.7) µV and (4.5 ± 0.7) µV, respectively(P < 0.05). After AIH stimulation, the enhanced respiratory intensity of rats in CIH group was much higher than that in the control group [(408 ± 149)% vs (242 ± 31)%, P < 0.05]. CONCLUSION: Both AIH and CIH can induce LTF of the hypoglossal nerve discharge, while the induction of LTF by AIH can be strengthened by CIH.