LAUSR

The main issue addressed here is the contribution of an enhancement of the expiratory modulation of sympathetic activity to the development of neurogenic hypertension in rats submitted to chronic intermittent hypoxia (CIH). Considering that active expiration associated with sympathetic overactivity was characterized in the in situ preparation of rats submitted to CIH, the specific question presented by O ́Connor, Lucking, and O ́Halloran (2019) in their recent Viewpoint was: is active expiration really contributing to sympathetic overactivity and hypertension in rats submitted to CIH? In previous studies using the in situ working heart–brainstem preparation of rats, we described how the 10 day CIH protocol induced active expiration and a simultaneous increase in sympathetic nerve activity (Moraes et al., 2013; Zoccal et al., 2008). We also described the presence of active expiration in conscious, freely moving rats, but in that study we were not aware of the incidence of active expiration in the different phases of the sleep–wake cycle (Moraes et al., 2013). In our recent study (Bazilio, Bonagamba, Moraes, & Machado, 2019), which was the focus of the Viewpoint by O ́Connor et al. (2019), we documented that the incidence of active expiration was higher in awake CIH-exposed hypertensive rats than in control animals (11 versus 3% of all respiratory cycles during wakefulness), but it was not observed in non-REM and REM sleep. It is also important to highlight some of our previous studies and concepts (Moraes et al., 2013) that are relevant in the context of this discussion: (i) sympathetic overactivity in rats exposed to CIH is not dependent on changes in the intrinsic electrophysiological properties of bulbospinal presympathetic neurons in the rostral ventrolateral medula (RVLM); (ii) CIH reduced the synaptic inhibition from ventral medullary respiratory neurons to the expiratory oscillator located in the parafacial respiratory group (pFRG); and (iii) pFRG expiratory neurons increase the frequency of discharge of RVLM presympathetic neurons and induce active expiration. Therefore, the question here is: to what extent does the occurrence of active expiration determine the development of sympathetic overactivity and neurogenic hypertension in CIH rats? In this context, the observed active expiration implies the presence of abdominal muscle activity and presumed expiratory-related sympathetic overactivity. However, we must consider the neuronal network involved in this respiratory–sympathetic coupling to draw a better picture of their interaction and its possible contribution to the development of neurogenic hypertension in rats exposed to CIH. It is