Comparative Assessment of Central and Peripheral Chemoreceptor Reflex Regulation of Muscle Sympathetic Nerve Activity and Ventilation

Abstract

We tested the hypothesis that central and peripheral chemoreceptor‐mediated sympathetic activation elicited by increases in CO2 tension (PCO2) mirror concurrent ventilatory responses. Twelve healthy young men (mean±SD; age: 24±4 yr; BMI: 24.5±1.3 kg·m−2) performed a modified rebreathing protocol designed to equilibrate central and peripheral chemoreceptor PCO2 tensions with end‐tidal PCO2 (PETCO2) at two isoxic end‐tidal PO2 (PETO2) tensions such that central chemoreceptor reflex responses (hyperoxia) can be isolated from additive peripheral responses (i.e., hypoxia minus hyperoxia). Subject's ventilation (volume turbine) and muscle sympathetic nerve activity (MSNA; microneurography, right fibular nerve) responses to rebreathing at isoxic PETO2 tensions of 150 mmHg (hyperoxia) and 50 mmHg (hypoxia) were recorded continuously. During rebreathing, the PETCO2 (mmHg) at which ventilation (L·min−1) and total MSNA (au) began to rise were identified as the PETCO2 recruitment thresholds (RT). Slopes of these responses above RT also were determined. In hyperoxic rebreathing (i.e., the central chemoreflex response), the mean RT for ventilation (46±3 mmHg) and MSNA (45±4 mmHg) did not differ (p>0.05). Mean slopes were 2.3±0.9 L·min−1·mmHg−1 and 2.1±1.5 au·mmHg−1, respectively. In hypoxic rebreathing (i.e., the summed central and peripheral chemoreflex response), the RT for both ventilation and MSNA were not different (41±3 mmHg vs 41±3 mmHg, p>0.05) but were lower (p<0.05) compared to hyperoxia. Mean slopes for ventilation (4.0±1.8 L·min−1·mmHg−1) and MSNA (5.1±3.4 au·mmHg−1) in hypoxia were greater than in hyperoxia yielding a mean peripheral chemoreflex sensitivity (hypoxic slope minus hyperoxic slope) of 1.7±0.1 L·min−1·mmHg−1 for ventilation and 3.0±2.6 au·mmHg−1 for MSNA. The 95% limits of agreement of RT between ventilation and MSNA for the central chemoreflex were −7 to 6 mmHg (bias=−1 mmHg, p>0.05) and −5 to 5 mmHg (bias=0 mmHg, p>0.05) for the peripheral chemoreflex. There was no relationship (p>0.05) between the ventilatory and MSNA sensitivity for either the central (r2=0.16) or peripheral (r2=0.01) chemoreceptor reflexes. These data highlight two novel findings: 1) ventilatory and sympathetic arms of the central and peripheral chemoreceptor reflexes are initiated at similar PETCO2 recruitment thresholds and 2) sympathetic responsiveness cannot be predicted from the sensitivities of the ventilatory central and peripheral chemoreceptor reflexes.Support or Funding InformationExperiments were funded by a Project Grant from the Canadian Institutes of Health Research (PJT 159491). Dr. Floras holds the Canada Research Chair in Integrative Cardiovascular Biology.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.