Brainstem PCO2 modulates phrenic responses to specific carotid body hypoxia in an in situ dual perfused rat preparation.
Inputs from central (brainstem) and peripheral (carotid body) respiratory chemoreceptors are coordinated to protect blood gases against potentially deleterious fluctuations. However, the mathematics of the steady-state interaction between chemoreceptors has been difficult to ascertain. Further, how this interaction affects time-dependent phenomena (in which chemoresponses depend upon previous experience) is largely unknown. To determine how central P(CO2) modulates the response to peripheral chemostimulation in the rat, we utilized an in situ arterially perfused, vagotomized, decerebrate preparation, in which central and peripheral chemoreceptors were perfused separately (i.e. dual perfused preparation (DPP)). We carried out two sets of experiments: in Experiment 1, we alternated steady-state brainstem P(CO2) between 25 and 50 Torr in each preparation, and applied specific carotid body hypoxia (60 Torr P(O2) and 40 Torr P(CO2)) under both conditions; in Experiment 2, we applied four 5 min bouts (separated by 5 min) of specific carotid body hypoxia (60 Torr P(O2) and 40 Torr P(CO2)) while holding the brainstem at either 30 Torr or 50 Torr P(CO2). We demonstrate that the level of brainstem P(CO2) modulates (a) the magnitude of the phrenic responses to a single step of specific carotid body hypoxia and (b) the magnitude of time-dependent phenomena. We report that the interaction between chemoreceptors is negative (i.e. hypo-additive), whereby a lower brainstem P(CO2) augments phrenic responses resulting from specific carotid body hypoxia. A negative interaction may underlie the pathophysiology of central sleep apnoea in populations that are chronically hypocapnic.
Day
Trevor A
TA
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Wilson
Richard J A
RJ
D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002245:Carbon Dioxide / Q000502:physiology*; D002344:Carotid Body / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology; D004594:Electrophysiology; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D008962:Models, Theoretical; D010791:Phrenic Nerve / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002245:Carbon Dioxide