A negative interaction between brainstem and peripheral respiratory chemoreceptors modulates peripheral chemoreflex magnitude

Abstract

Interaction between central (brainstem) and peripheral (carotid body) respiratory chemosensitivity is vital to protect blood gases against potentially deleterious fluctuations, especially during sleep. Previously, using an in situ arterially perfused, vagotomized, decerebrate preparation in which brainstem and peripheral chemoreceptors are perfused separately (i.e. dual perfused preparation; DPP), we observed that the phrenic response to specific carotid body hypoxia was larger when the brainstem was held at 25 Torr PCO2 compared to 50 Torr PCO2. This suggests a negative (i.e. hypo-additive) interaction between chemoreceptors. The current study was designed to (a) determine whether this observation could be generalized to all carotid body stimuli, and (b) exclude the possibility that the hypo-additive response was the simple consequence of ventilatory saturation at high brainstem PCO2. Specifically, we tested how steady-state brainstem PCO2 modulates peripheral chemoreflex magnitude in response to carotid body PCO2 and PO2 perturbations, both above and below eupnoeic levels. We found that the peripheral chemoreflex was more responsive the lower the brainstem PCO2 regardless of whether the peripheral chemoreceptors received stimuli which increased or decreased activation. These findings demonstrate a negative interaction between brainstem and peripheral chemosensitivity in the rat in the absence of ventilatory saturation. We suggest that a negative interaction in humans may contribute to increased controller gain associated with sleep-related breathing disorders and propose that the assumption of simple addition between chemoreceptor inputs used in current models of the respiratory control system be reconsidered. © Journal compilation © 2009 The Physiological Society.