Glutamatergic transmission is altered in the caudal NTS of rats submitted to chronic intermittent hypoxia

Abstract

We hypothesize that chronic intermittent hypoxia (CIH) alters the glutamatergic mechanisms in neurons of the caudal aspect of nucleus of tractus solitarius (cNTS) of rats. Using in situ working heart‐brainstem preparations of rats submitted to CIH (6% O2, for 40 s every 9 min, 8 h/day; n=9) or normoxia (control, n=7) for 10 days, basal and chemoreflex‐induced changes in phrenic and sympathetic nerve activities were evaluated after microinjections of kynurenic acid (KYN, 250 mM) in the cNTS. KYN in the cNTS produced large increases in phrenic burst frequency (0.3±0.1 vs 0.8±0.1 Hz) and duration (0.6±0.1 vs 0.9±0.1 s) in control rats, while in CIH rats the increase in the frequency was smaller (0.3±0.1 vs 0.6±0.1 Hz) and no changes were observed in the duration (0.6±0.1 vs 0.7±0.1 sec). Besides, the sympathoexcitatory response to chemoreflex activation (KCN, 0.05%) was reduced in control rats (90±11 vs 56±6 %), but not in CIH rats (112±9 vs 119±10 %) after KYN in the cNTS, whilst no changes were observed in the tachypneic response in both groups. Accordingly, the expression of NMDAR1 in the cNTS, examined by immunoblotting, was higher in CIH (n=3) than in control rats (n=3)(p=0.02). Altogether, the data suggest that glutamatergic neurotransmission in the cNTS is increased after CIH exposure, which may contribute to the respiratory and sympathetic dysfunctions observed in this experimental model. Supported by FAPESP and CNPq.