Hypoxia‐induced sympathetic long‐term facilitation is mediated by a rightward shift in sympathetic action potential amplitude distribution and baroreflex resetting of action potential clusters
Authors: Shafer Brooke , Incognito Anthony , Vermeulen Tyler , Nardone Massimo , Teixeira Andre , Klassen Stephen , Millar Philip , Foster Glen 
Published: May 2022

Introduction

Baroreflex resetting permits sympathetic long‐term facilitation (sLTF) following hypoxia. Muscle sympathetic nerve activity (MSNA) bursts are generated by synchronous discharge of varying‐amplitude action potentials (APs), with medium APs under strong baroreflex control. AP discharge strategies and baroreflex control of AP clusters facilitating sLTF is unknown. We hypothesized that recruitment of previously latent, large‐amplitude APs and baroreflex resetting of AP cluster operating points (OPs) would mediate sLTF following acute hypoxia.

Methods

Eight men (age = 24±3 yrs; BMI = 24±3 kg/m2) were exposed to 20 min isocapnic hypoxia (PETO2: 47±2 mmHg) and 30 min recovery. Blood pressure (BP; photoplethysmography) and MSNA (fibular microneurography) were acquired during baseline, hypoxia, early (first 5‐min) and late recovery (last 5‐min). Multi‐unit MSNA burst frequency (BF) and total activity (TA) were quantified. A continuous wavelet transform with matched mother wavelet was used to extract sympathetic APs. AP frequency, AP amplitude (normalized % of largest baseline AP amplitude), percent APs occurring outside a MSNA burst (% asynchronous APs) and total AP clusters was calculated. The proportion of APs firing in small (1‐3), medium (4‐6) and large (7‐10) normalized cluster sizes was assessed. Baroreflex OP was measured by plotting the intersection point of mean cluster incidence and mean diastolic BP (DBP). Friedman repeated‐measures analysis of variance on ranks was used to determine the effect of condition (baseline, hypoxia, early, late). Data are means ± standard deviation or 95% confidence intervals.

Results

Hypoxia increased BF (P<0.01), TA (P<0.01), AP frequency (Δ124{‐30, 279} AP/min, P<0.05), AP amplitude (Δ3{1, 5} %, P<0.05) and decreased asynchronous APs (Δ‐10{‐17, ‐4} %, P<0.03). Compared to baseline, BF (P<0.03), TA (P<0.02) and AP amplitude (early: Δ3{0, 5} %, P<0.05; late: Δ4{1, 6} %, P<0.05) was elevated during recovery while asynchronous APs (early: Δ‐9{‐16, ‐3} %, P<0.03; late: Δ‐7{‐14, ‐1} %, P<0.03) were reduced. The total number of AP clusters was increased (P<0.05) with no one condition different compared to baseline (hypoxia: Δ3{‐1, 7} clusters; early and late: Δ3{‐1, 6} clusters, P>0.10). Proportion of APs in small clusters was reduced in hypoxia (hypoxia: 44±18 %, P<0.05), early (46±21 %, P<0.05) and late recovery (44±17 %, P<0.05) compared with baseline (53±20 %) while the proportion of APs in large clusters was increased in early recovery (7±6 %, P<0.05) compared with baseline (5±5 %). Baroreflex OPs were shifted rightward for all AP clusters in recovery (baseline DBP: 63±5; early DBP: 64±5; late DBP: 65±4, mmHg; P<0.05) with no effect on slope (P>0.20).

Conclusions

Hypoxia‐induced sLTF is mediated by reduced asynchronous AP firing, a proportional shift toward large‐amplitude AP activity, and baroreflex resetting of AP clusters to higher OPs.