Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRC(Apnea)) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRC(Apnea)) hemoglobin saturation (HbSat) levels (RBR(Matched)) or more severe levels (RBR(End)). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBR(ALT)). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBR(Matched) was associated with reduced AP frequency and APs per burst compared with FRC(Apnea) (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRC(Apnea) (+10 ± 2; P < 0.001) but not during RBR(Matched) (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBR(End) (HbSat: 56 ± 13 vs. 71 ± 6%; P < 0.001), RBR(End) was associated with a restrained increase in the APs per burst (FRC(Apnea): +18 ± 7; RBR(End): +11 ± 5) and total AP clusters (FRC(Apnea): +10 ± 2; RBR(End): +6 ± 4) (both P < 0.01). During FRC-RBR(ALT), all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.