At rest, inspiration is an active process while expiration is passive. However, high chemical drive (hypercapnia or hypoxia) activates central and peripheral chemoreceptors triggering reflex increases in inspiration and active expiration. The Locus Coeruleus contains noradrenergic neurons (A6 neurons) that increase their firing frequency when exposed to hypercapnia and hypoxia. Using recently developed neuronal hyperpolarising technology in conscious rats, we tested the hypothesis that A6 neurons are a part of a vigilance centre for controlling breathing under high chemical drive and that this includes recruitment of active inspiration and expiration in readiness for flight or fight. Pharmacogenetic inhibition of A6 neurons was without effect on resting and on peripheral chemoreceptors-evoked inspiratory, expiratory and ventilatory responses. On the other hand, the number of sighs evoked by systemic hypoxia was reduced. In the absence of peripheral chemoreceptors, inhibition of A6 neurons during hypercapnia did not affect sighing, but reduced both the magnitude and incidence of active expiration, and the frequency and amplitude of inspiration. These changes reduced pulmonary ventilation. Our data indicated that A6 neurons exert a CO2-dependent modulation of expiratory drive. The data also demonstrate that A6 neurons contribute to the CO2-evoked increases in the inspiratory motor output and hypoxia-evoked sighing.

The carotid bodies are peripheral chemoreceptors and contribute to the homeostatic maintenance of arterial levels of O, CO and [H]. They have attracted much clinical interest recently because of the realisation that aberrant signalling in these organs is associated with several pathologies including hypertension. Herein, we describe data suggesting that sympathetic overactivity in neurogenic hypertension is, at least in part, dependent on carotid body tonicity and hyperreflexia that is related to changes in the electrophysiological properties of chemoreceptive petrosal neurons. We present results showing critical roles for both ATP levels in the carotid bodies and expression of P2X3 receptors in petrosal chemoreceptive, but not baroreceptive, terminals in the aetiology of carotid body tonicity and hyperreflexia. We discuss mechanisms that may underlie the changes in electrophysiological properties and P2X3 receptor expression in chemoreceptive petrosal neurons, as well as factors affecting ATP release by cells within the carotid bodies. Our findings support the notion of targeting the carotid bodies to reduce sympathetic outflow and arterial pressure, emphasizing the potential clinical importance of modulating purinergic transmission to treat pathologies associated with carotid body dysfunction, but, importantly, sparing physiological chemoreflex function.

Exercise involves the interaction of several physiological processes, in which adjustments in pulmonary ventilation occur in response to increased O 2 consumption, CO 2 production and altered acid-base equilibrium. The peripheral chemoreceptors (carotid bodies; CBs) are sensitive to changes in the chemical composition of arterial blood, and their activation induces active inspiratory and expiratory responses. Herein, we tested the hypothesis that the CBs contribute to the active inspiratory and expiratory responses to exercise in rats. We performed electromyographic recordings of the diaphragm (Dia EMG) and abdominal internal oblique (Abd EMG) muscles in rats before and after bilateral removal of the CBs (CBX) during constant-load low-intensity and high-intensity progressive treadmill exercise. We also collected arterial blood samples for gaseous and pH analyses. Similar increases in Dia EMG frequency in both experimental conditions (before and after CBX) during low-intensity exercise were observed, without significant changes in the Dia EMG amplitude. During high-intensity exercise, lower responses of both Dia EMG frequency and Dia EMG amplitude were observed in rats after CBX. The Abd EMG phasic active expiratory response was not significant either before or after CBX during low-intensity exercise. However, CBX reduced the phasic active expiratory responses during high-intensity exercise. The blunted responses of inspiratory and expiratory adjustments to high-intensity exercise after CBX were associated with higher P aCO 2 levels and lower arterial pH values. Our data show that in rats the CBs do not participate in the inspiratory and expiratory responses to low-intensity exercise, but are involved in the respiratory compensation against the metabolic acidosis induced by high-intensity exercise.

No abstract

Aims Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory‐related sympathetic bursting. Activation of catecholaminergic C1 neurones induces sympathoexcitation, while its ablation reduces the chemoreflex sympathoexcitatory response. However, no study has determined the respiratory phase(s) in which the pre‐sympathetic C1 neurones are recruited by peripheral chemoreceptor and whether C1 neurone activation affects all phases of respiratory modulation of sympathetic activity. We addressed these unknowns by testing the hypothesis that peripheral chemoreceptor activation excites pre‐sympathetic C1 neurones during inspiration and expiration. Methods Using the in situ preparation of rat, we made intracellular recordings from baroreceptive pre‐sympathetic C1 neurones during peripheral chemoreflex stimulation. We optogenetically activated C1 neurones selectively and compared any respiratory‐phase‐related increases in sympathetic activity with that which occurs following stimulation of the peripheral chemoreflex. Results Activation of peripheral chemoreceptors using cytotoxic hypoxia (potassium cyanide) increased the firing frequency of C1 neurones and both the frequency and amplitude of their excitatory post‐synaptic currents during the phase of expiration only. In contrast, optogenetic stimulation of C1 neurones activates inspiratory neurones, which secondarily inhibit expiratory neurones, but produced comparable increases in sympathetic activity across all phases of respiration. Conclusion Our data reveal that the peripheral chemoreceptor‐mediated expiratory‐related sympathoexcitation is mediated through excitation of expiratory neurones antecedent to C1 pre‐sympathetic neurones; these may be found in the Kölliker‐Fuse nucleus. Despite peripheral chemoreceptor excitation of inspiratory neurones, these do not trigger C1 neurone‐mediated increases in sympathetic activity. These studies provide compelling novel insights into the functional organization of respiratory–sympathetic neural networks.