Carotid chemoreflex inhibition improves neural cardiovascular control in women with rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular risk, which is potentially exacerbated by impaired neural cardiovascular control, including increased sympathovagal balance and blood pressure (BP) variability as well as reduced baroreflex sensitivity (BRS). The mechanisms underlying this impaired neurocardiovascular control in RA remain poorly understood. Emerging evidence from preclinical studies suggests that inflammatory conditions (such as in RA) may exacerbate the activity of oxygen-sensitive carotid chemoreceptors, potentially driving altered neural efferent cardiovascular responses. If true, inhibition of the carotid chemoreflex activity using hyperoxia should improve markers of neural cardiovascular control in RA, a hypothesis that has yet to be tested. Objectives: To investigate whether carotid chemoreflex inhibition using hyperoxia improves cardiovascular autonomic control in women with RA. Methods: Ten women with RA (51±8years) attended the laboratory to undergo assessments of cardiovascular autonomic control during normoxic (21%FiO2; control) and hyperoxic (100%FiO2; chemoreflex inhibition) conditions. A group of 10 non-RA controls (45±10years) also performed normoxic assessments for baseline comparisons. Cardiovascular autonomic control was assessed via the continuous recording of beat-by-beat heart rate and BP at rest, followed by the subsequent analysis of: a) sympathovagal balance via spectral analysis of heart rate variability (and quantification of high-frequency [HF-RR] and the low-frequency to high-frequency ratio [LF/HF]); b) BP variability (via spectral analysis of systolic BP and quantification of LF-SBP); and c) BRS (using the sequence method to quantify the gain of all spontaneous baroreflex sequences). Results: As expected, during normoxic conditions, individuals with RA demonstrated increased sympathovagal balance (HF = 316.05 ± 127.65 vs 962.82 ± 828.86 ms 2 , P =0.05; LF/HF = 0.77 ± 0.43 vs 0.40 ± 0.21, P =0.05), increased BP variability (LF-SBP = 14.32 ± 11.47 vs, 5.48 ± 2.90 mmHg 2 , P =0.03) and reduced BRS (BRS gain = 7.46 ± 2.17 vs 14.13 ± 7.03 ms/mmHg, P=0.01), when compared to controls. Inhibition of the carotid chemoreflex with hyperoxia reduced BP variability (∆LF-SBP = -4.15 ± 3.80mmHg 2 ; P =0.02) and increased BRS (∆BRS gain = +1.45 ± 1.32 ms/mmHg, P <0.01), with evidence of normalization for these outcomes (i.e., not different from non-RA control). Conclusion: The results of this study indicate that inhibition of the carotid chemoreflex with hyperoxia significantly improves neural cardiovascular control in RA. This data gives support to the hypothesis that chemoreflex activity is increased in RA. Future studies should further explore whether these alterations in neurocardiovascular control are driven by systemic or carotid body inflammation, aiming to develop targeted interventions that can mitigate the heightened chemoreflex sensitivity and improve cardiovascular function in individuals with RA. The São Paulo Research Foundation, regular programs doctorate scholarship: 2022/08603-5; Federal Agency for Support and Evaluation of Graduate Education. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.