Peripheral chemoreceptors and cardiorespiratory coupling: a link to sympatho‐excitation

Abstract

Chronic intermittent hypoxia (CIH) has been identified as a relevant risk factor for the development of enhanced sympathetic outflow and arterial hypertension. Several studies have highlighted the importance of peripheral chemoreceptors for the cardiovascular changes elicited by CIH. However, the effects of CIH on the central mechanisms regulating sympathetic outflow are not fully elucidated. Our research group has explored the hypothesis that the enhanced sympathetic drive following CIH exposure is, at least in part, dependent on alterations in the respiratory network and its interaction with the sympathetic nervous system. In this report, I discuss the changes in the discharge profile of baseline sympathetic activity in rats exposed to CIH, their association with the generation of active expiration and the interactions between expiratory and sympathetic neurones after CIH conditioning. Together, these findings are consistent with the theory that mechanisms of central respiratory–sympathetic coupling are a novel factor in the development of neurogenic hypertension.

Chemoreception and neuroplasticity in respiratory circuits

“…On the other hand, experimental evidence in SHR suggests that the pre-I/I population in the pre-BötC becomes more excitable via a decrease in leak conductance (Moraes et al, 2014). We use this evidence to formulate the hypothesis that repetitive activation of peripheral and, hence, central chemoreceptors during CIH conditioning induces plasticity in this population as recently proposed (Moraes et al, 2015, Zoccal, 2015); specifically, we model the respiratory plasticity evoked by CIH as a decrease in the leak conductance of the pre-I/I population. The average leak conductance of these neurons was decreased from 2.9 nS in the control model to 2.3 nS in the CIH model.…”

Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach

“…Second, although several studies have stressed the importance of peripheral chemoreceptors for hypertensive risk in models of IH, an enhanced sympathetic outflow may also be derived on alteration of the link between respiratory networks and sympathetic activation. As shown by the results of Zoccal in rat models,91 expiratory neurons located in the parafacial respiratory group might be activated by central chemoreflexes inducing an increase of expiratory parafacial respiratory group neurons that drive sympathetic overactivity in rats exposed to CIH. These results open discussion on the role of the interaction between expiratory activity and sympathetic activity in occurrence and persistence of arterial HT in animals exposed to CIH.…”

“…The altered balances between cardioprotective parasympathetic activity and enhanced sympathetic tonus result in tachycardia, decreased baroreflex sensitivity, and a rise in BP and cardiovascular risk 89. These consequences are explained by the effect of GABAergic mechanisms that exert an inhibitory effect on parasympathetic cardiac vagal neurons,90 and orexin-A acting on parasympathetic control of the heart rate 91. The effect of decreased baroreceptor activity and plasma levels of orexin-A92 and its consequences on BP control has also been demonstrated in OSA patients 93…”

Finding inspiration in high blood pressure

“…). As acknowledged by Zoccal (), ‘the CIH model does not reproduce the pathophysiology of OSA’, but he then goes on to state that ‘these clinical data [of Fatouleh et al . ] parallel our experimental observations, highlighting that changes in the respiratory–sympathetic coupling mechanisms may be considered relevant to the development of arterial hypertension associated with CIH exposure’.…”