Central chemoreflex sensitivity is augmented in treated human hypertension
Authors: Sayegh Ana Luiza , Fan Jui-Lin , Dawes Mathew , Paton Julian , Fisher James 
Published: May 2023

Hypertension (HTN) is an independent risk factor for cardiovascular disease and stroke, but the underlying pathogenesis is incompletely understood. In animal models heightened central chemoreflex sensitivity is associated with HTN, sympatho-excitation and end-organ damage. Moreover, increased chemosensitivity to hypercapnia and hypoxia (i.e., combined central plus peripheral chemoreflex activation) is associated with poor outcomes in heart failure patients. Herein, we sought to determine whether central, and combined central plus peripheral, chemoreflex sensitivities are augmented in human HTN. Twenty eight volunteers (15 HTN, 13 normotension [NT]) performed two modified rebreathing protocols where the partial pressure of end-tidal carbon dioxide (PETCO2) progressively increased while the partial pressure of end-tidal oxygen (PETO2) was clamped at: 1) 150 mmHg (isoxic hyperoxic rebreathing; central chemoreflex activation) and 2) 50 mmHg (isoxic hypoxic rebreathing; combined central plus peripheral chemoreflex activation). Blood pressure (BP), muscle sympathetic nerve activity (MSNA) and ventilation (V̇E) were recorded. Chemoreflex sensitivity was calculated as MSNA vs. PETCO2slope (sympathetic chemoreflex sensitivity) and V̇E vs. PETCO2slope (ventilatory chemoreflex sensitivity). The sympathetic and ventilatory recruitment thresholds were taken as the PETCO2breakpoint at which MSNA and V̇E started to increase during rebreathing. HTN and NT groups were closely matched for age (68±5 vs. 65±6 years; P=0.100; mean±SD) and sex (women, 7 (47%) vs. 8 (62%); P=0.332). Resting systolic (153±15 vs. 123±17 mmHg; P<0.001) and diastolic (86±9 vs. 77±7 mmHg; P=0.043) BP were higher in HTN, while MSNA (27±5 vs. 25±7 bursts·min-1; P=0.723) and V̇E (13.1±3.8 vs. 12.5±2.5 L·min-1; P=0.872) were not different. Central sympathetic (3.32±1.90 vs. 1.77±0.62 a.u.·mmHg-1; P=0.034) and ventilatory (2.48±1.33 vs. 1.58±0.42 L·min-1·mmHg-1; P=0.030) chemoreflex sensitivities were greater in HTN. In contrast, there were no between-group differences in combined central plus peripheral sympathetic (P=0.831) and ventilatory (P=0.284) chemoreflex sensitivities. Sympathetic and ventilatory recruitment thresholds during central chemoreflex activation, and combined central plus ventilatory chemoreflex activation, did not differ between HTN and NT groups (all P>0.05). In summary, central ventilatory and sympathetic chemoreflex sensitivities are augmented in human HTN. Future studies are now required to reduce central chemoreflex sensitivity and assess whether this provides a novel approach to lower BP in HTN patients. Support was provided by the Auckland Medical Research Foundation (Ref# 1119008. JPF, JFRP, ALCS), the Health Research Council of New Zealand (Ref# 19/687. JPF, JFRP), and the Sidney Taylor Trust (JFRP). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.