Within-breath sympathetic baroreflex sensitivity is modulated by lung volume but unaffected by acute intermittent hypercapnic hypoxia in men

Muscle sympathetic nerve activity (MSNA) exhibits well-described within-breath respiratory modulation, but the interactive contributions of the arterial baroreflex remain unclear. The present study assessed 1) within-breath modulation of sympathetic baroreflex sensitivity (BRS) and 2) the effect of acute intermittent hypercapnic hypoxia (IHH) on within-breath sympathetic BRS and respiratory-sympathetic entrainment. Seventeen men (24 +/- 4 yr) underwent an 8- to 10-min spontaneously breathing baseline while continuous measures of blood pressure (BP), heart rate, MSNA, ventilation, and end-tidal gases were collected. A subset of 12 participants subsequently underwent a 40-min IHH exposure composed of 40 consecutive 1-min breathing cycles: 40 s of hypercapnic hypoxia and 20 s of normoxia. Data were compared between inspiration and expiration and low and high lung volume (calculated from the integral of spirometry-derived flow). Sympathetic BRS was determined by the slope of the weighted linear regression between diastolic BP and MSNA burst incidence. Respiratory-sympathetic entrainment was quantified as percentage of MSNA bursts during each respiratory epoch relative to the total burst count. Sympathetic BRS was similar between inspiration and expiration (-3.9 +/- 2.0 vs. -3.6 +/- 1.8 bursts.100 heartbeats(-1).mmHg(-1); P = 0.61) but greater during low versus high lung volumes (-4.6 +/- 2.3 vs. -2.1 +/- 1.6 bursts.100 heartbeats(-1).mmHg(-1); P < 0.01). High (r = -0.64; P < 0.01)- but not low (r = -0.24; P = 0.35)-lung volume sympathetic BRS was associated with resting MSNA. IHH increased resting MSNA burst frequency (15 +/- 7 vs. 20 +/- 7 bursts/min; P < 0.01) and diastolic BP (68 +/- 5 vs. 77 +/- 9 mmHg; P = 0.02), without altering resting or within-breath sympathetic BRS or respiratory-sympathetic entrainment (all P > 0.05). These findings provide novel insight into the mechanisms controlling within-breath modulation of sympathetic outflow in humans. NEW & NOTEWORTHY In resting spontaneously breathing men. the present study observed that sympathetic barorefiex sensitivity (BRS) was higher during low versus high lung volumes but not different between inspiration and expiration. I ligh- but not low-lung volume BRS was negatively associated with resting muscle sympathetic nerve activity (MSNA). Acute intermittent hypercapnic hypoxia increased resting MSNA and diastolic blood pressure, without altering within-breath BRS. These findings provide novel insight into mechanisms controlling within-breath modulation of MSNA in humans.