Iannarelli, Nathan

Our knowledge regarding baroreflex regulation of subpopulations of differently sized sympathetic action potentials (APs) remains incomplete. This study tested the hypothesis that baroreflex sigmoid morphology varies across AP subpopulations. In 12 healthy individuals (6 females; 32 ± 5 years), we measured diastolic blood pressure (DBP; brachial artery catheter) and muscle sympathetic APs (peroneal microneurography; continuous wavelet transform) during a modified Oxford protocol (100 μg nitroprusside bolus, 150 μg phenylephrine bolus). Baroreflex sigmoids (four-parameter logistic functions) modelled the relationship between DBP and sympathetic AP discharge probability for 10 normalized AP clusters. For each AP cluster, baroreflex sigmoid morphology was quantified by max gain, threshold, centering, and saturation pressures, and operating and response ranges. One-way analyses of variance and Dunnett post-hoc tests were performed. Data are mean ± SD. At the centering pressure of the baroreflex sigmoid, max gain was greater for medium APs (e.g., Cluster 3: -5.6 ± 2.9%/mmHg) compared to small (e.g., Cluster 1: -1.4 ± 1.1%/mmHg; P < 0.01) and large APs (e.g., Cluster 9: -0.6 ± 0.4%/mmHg; P < 0.01). Discharge probability at the centering pressure was also greater for medium APs (e.g., Cluster 3: 61 ± 22%) compared to small (e.g., Cluster 1: 12 ± 10%; P < 0.01) and large APs (e.g., Cluster 9: 3 ± 3%; P < 0.01). There were no differences in the saturation pressure (i.e., DBP where any further reduction does not elicit an increase in AP discharge probability) between AP clusters (main effect P = 0.22). The threshold pressure (i.e., DBP where any further reductions elicit an increase in AP discharge probability) was greater for medium (e.g., Cluster 3: 78 ± 8mmHg) compared to large APs (e.g., Cluster 9: 74 ± 11mmHg; P = 0.03). The operating range (i.e., Threshold – Saturation DBP) was greater for medium (e.g., Cluster 3: 14 ± 3mmHg) compared to large APs (e.g., Cluster 9: 8 ± 5mmHg; P < 0.01). There were no differences in the threshold pressure or operating range of medium compared to small APs (both P ≥ 0.82). The response range (i.e., Saturation – Threshold discharge probability) was greater for medium (e.g., Cluster 3: 26 ± 13%) compared to small (e.g., Cluster 1: 5 ± 4%; P < 0.01) and large APs (e.g., Cluster 9: 1 ± 1%; P < 0.01). These data confirm prior work using linear modeling and spontaneous approaches to quantify sympathetic AP baroreflex gain and extend to demonstrate variation in the morphology of the baroreflex sigmoid. During large changes in blood pressures, we identify differences in broader features of baroreflex control (e.g., threshold pressure, operating range, and response range) between AP subpopulations that support strong baroreflex regulation over medium-sized APs. This abstract was presented at the American Physiology Summit 2026 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.

This study aimed to investigate the impact of central α2-adrenergic mechanisms on arterial baroreflex control of sympathetic and cardiovagal outflow in healthy humans. R-R interval (ECG), blood pressure (brachial arterial catheter), and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were measured in eight healthy participants (5 females; 28±7 years). Sympathetic action potentials (AP) were extracted from the filtered MSNA neurogram (continuous wavelet transform) during a 5-minute baseline (BSL) and an intravenous dexmedetomidine infusion consisting of a loading dose (LD; 10 minutes at 0.225 μg/kg/hr) and a maintenance dose (MD; ~0.15 μg/kg/hr). Sympathetic AP baroreflex threshold gain was measured as the slope of the linear relationship between AP discharge probability and diastolic blood pressure. The linear relationship between R-R interval and systolic blood pressure (sequence technique) quantified cardiovagal baroreflex gain. Mixed-effects analyses and post-hoc t-tests were performed. Data are reported as mean ± SD. Dexmedetomidine reset the baroreflex threshold operating points for all sympathetic AP clusters downwards to lower firing probabilities (cluster 4; BSL: 20±6, LD: 13±8, MD: 6±5%, both p<0.01 vs. BSL) and leftwards to lower diastolic pressures (BSL: 72±9, LD: 69±8, MD: 65±10 mmHg, both p<0.01 vs. BSL). Dexmedetomidine reduced baroreflex threshold gain for the subpopulation of medium-sized sympathetic APs (cluster 4; BSL: -6.5±2.0, LD: -2.6±1.6, MD: -2.0±0.7 %/mmHg, both p<0.01 vs. BSL). Dexmedetomidine did not affect baroreflex threshold gain of small (cluster 1; BSL: -1.9±1.1, LD: -1.3±1.6, MD: -1.1±0.8 %/mmHg, both P>0.88 vs. BSL) or large AP clusters (cluster 9; BSL: -0.8±0.4, LD: -0.8±1.0, MD: -0.2±0.7 %/mmHg, both P>0.98 vs. BSL). Dexmedetomidine reset the cardiovagal baroreflex to lower systolic pressures but did not affect R-R interval (BSL: 1035±261, LD: 1025±308, MD: 1005±292ms, Main effect P=0.45) or gain (BSL: 24±11, LD: 30±20, MD: 26±25 ms/mmHg, Main effect P=0.63). These findings suggest that central α2-adrenergic mechanisms differentially affect arterial baroreflex control of sympathetic and cardiovagal outflow in humans by minimally affecting cardiovagal baroreflex gain but strongly affecting the baroreflex gain for the subpopulation of medium-sized sympathetic APs. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

This study investigated the impact of integrated muscle sympathetic nerve activity (MSNA) discharge patterns on human neurocirculatory regulation. In 13 healthy females (42 ± 15 years), the transduction of integrated MSNA (peroneal microneurography) into mean arterial pressure (MAP; arterial catheter) was studied during an intravenous infusion of a nicotinic ganglionic antagonist (trimethaphan camsylate, 1-7 mg/min). Neurovascular transduction (signal averaging) was studied based on the overall response, burst sequence (singlet, doublet, and triplet+), and burst amplitude (binned into tertials: small, medium, and large bursts). Data (mean ± SD) are reported for a 10-minute baseline (BSL), the one-minute period at the midpoint of the trimethaphan infusion with integrated MSNA bursts (TM-Mid), and the last minute of trimethaphan infusion with integrated MSNA bursts (TM-Last). During BSL, the MAP transduction responses were greatest for triplets+ (singlets: 0.9 ± 0.2 mmHg, doublets: 2.0 ± 0.6 mmHg, triplet+: 2.6 ± 0.9 mmHg; P < 0.01) and large bursts (small: 1.0 ± 0.3 mmHg, medium: 1.7 ± 0.5 mmHg, large: 2.2 ± 0.7 mmHg; P < 0.01). Trimethaphan infusion reduced integrated MSNA burst frequency resulting in a greater proportion of singlets (BSL: 45 ± 18 %, TM-Mid: 75 ± 23 %, TM-Last: 94 ± 20 %; P < 0.01), a lower proportion of doublets, and a lower proportion of triplets+ (BSL: 23 ± 19 %, TM-Mid: 9 ± 18 %, TM-Last: 0 ± 0 %; P < 0.01). Trimethaphan infusion reduced integrated MSNA burst amplitude resulting in a greater proportion of small bursts (BSL: 33 ± 0.2 %, TM-Mid: 60 ± 26 %, TM-Last: 78 ± 37 %; P < 0.01), a lower proportion of medium bursts, and a lower proportion of large bursts (BSL: 34 ± 1 %, TM-Mid: 17 ± 26 %, TM-Last: 1 ± 5 %; P < 0.01). Trimethaphan-mediated changes in MSNA burst frequency and amplitude were associated with reduced overall MAP transduction responses (BSL: 1.6 ± 0.5 mmHg, TM-Mid: 0.5 ± 0.2 mmHg, TM-Last: 0.3 ± 0.3 mmHg; P < 0.01). Linear regression analyses demonstrated that the trimethaphan-mediated reduction in the proportion of large bursts ( β = 0.02 ± 0.008 mmHg/%, R2 = 0.13, P = 0.03) more strongly affected sympathetic neurovascular transduction responses than reductions in the proportion of triplet+ burst sequences (P = 0.91). These findings suggest that time varying MSNA discharge patterns, particularly variations in burst amplitude, support human neurocirculatory regulation. This work was supported by the National Institutes of Health and the Natural Sciences and Engineering Research Council of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.