Respiratory modulation of sympathetic activity during hypoxia in adults with overweight and obesity

We examined the relationship between ventilation and muscle sympathetic nerve activity (MSNA) in adults with overweight/obesity under normoxic and hypoxic conditions. We hypothesized hypoxia would augment respiratory modulation of MSNA, with greater effects in adults with overweight/obesity versus normal weight controls. MSNA and minute ventilation were evaluated in adults with normal weight (8 F/12 M, 23 ± 2 kg·m^-2) and overweight/obesity (6 F/2 M, 35 ± 5 kg·m^-2) during normoxia (10 min, 97 ± 1% [Formula: see text]) and steady-state hypoxia (5 min, 82 ± 2% [Formula: see text]). Respiratory modulation of MSNA was assessed via cross-correlation histograms between MSNA spikes and respiration, and the modulation index (MI) was calculated as the relative difference between the maximum and minimum number of MSNA spikes across the breath. Adults with obesity had greater minute ventilation (P = 0.049) and MSNA frequency (P = 0.013) than normal-weight adults. Hypoxia increased minute ventilation (P < 0.001) and MSNA (P = 0.007) in both groups. MI increased with hypoxia in adults with obesity (57 ± 16% to 76 ± 14%, P = 0.005) but not in adults with normal weight (61 ± 14% to 66 ± 17%, P = 0.333). During hypoxia, group differences in normalized MSNA were most apparent during early inspiration, whereby MSNA was greater in normal weight versus obesity (P = 0.014). Adults with overweight/obesity exhibit enhanced inspiratory sympathoinhibition during hypoxia, resulting in amplified respiratory-sympathetic coupling.NEW & NOTEWORTHY Muscle sympathetic nerve activity (MSNA) is modulated by respiration, with MSNA greatest during end-expiration (low lung volume) and lowest at peak inspiration (high lung volume). Adults with overweight/obesity exhibit enhanced inspiratory sympathoinhibition during hypoxia, resulting in amplified respiratory-sympathetic coupling, compared with adults of normal weight. Findings underscore the early implications of obesity on sympathetic activity during hypoxia before the development of overt disease (i.e., sleep apnea, chronic obstructive pulmonary disease).