Citations

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.

Intravenous dexmedetomidine infusion (selective α 2 -adrenergic receptor agonist) 1) reduced the firing probability and strength of baroreflex control over medium-sized sympathetic action potentials in muscle sympathetic nerve activity (MSNA) and 2) attenuated the transduction of MSNA bursts to changes in blood pressure (BP) by reducing the magnitude of BP responses and increasing the time to peak BP. These data suggest that neural and vascular α 2 -adrenergic mechanisms contribute to sympathetic baroreflex regulation of human BP.

Sympathetic control of human blood pressure is mechanistically regulated by α 2 -adrenergic receptors distributed throughout the nervous system and cardiovascular end-targets. Recently, we discovered the sympathoinhibitory effects of central α 2 -adrenergic mechanisms on human sympathetic neuronal emission patterns. However, our knowledge remains incomplete regarding the impact of α 2 -adrenergic mechanisms on beat-by-beat transduction of muscle sympathetic nerve activity (MSNA) bursts to changes in blood pressure and heart rate (HR). Based on evidence of α 2 -adrenergic receptors within central and peripheral sympathetic neural sites and on the vasculature, this study tested the hypothesis that activation of α 2 -adrenergic receptors with dexmedetomidine (DEX) would reduce sympathetic transduction to blood pressure. In eight healthy participants (5 females; 28 ± 7 years), diastolic blood pressure (DBP; brachial arterial catheter), HR (ECG), and MSNA (peroneal microneurography) were recorded during a 5-minute supine baseline (BSL) and an intravenous DEX infusion consisting of a loading dose (10 minutes at 0.225 μg/kg/hr) and a maintenance dose (~0.15 μg/kg/hr). Signal averaging quantified sympathetic transduction to DBP and HR for 12 cardiac cycles following integrated MSNA bursts. We also quantified sympathetic transduction to DBP using a transduction gain estimate derived from the slope of the linear relationship between the peak DBP response and the number of cardiac cycles until peak DBP response. Data (mean ± SD) are reported for the 5-minute BSL and the last 5-minute period during the DEX infusion. Mixed-effects modeling and t -tests were performed. Non-parametric tests were performed for non-normally distributed data. DEX reduced resting MAP (BSL: 92 ± 7, DEX: 82 ± 6 mmHg: p < 0.001) but did not affect resting HR (BSL: 62 ± 14, DEX: 61 ± 14 bpm; p = 0.853). DEX reduced resting integrated MSNA burst frequency (BSL: 14 ± 6, DEX: 4 ± 3 bursts/min; p = 0.001) and total integrated MSNA (BSL: 663 ± 252, DEX: 188 ± 142 AU/min; p < 0.001). DEX attenuated the DBP transduction response, particularly for the cardiac cycle associated with peak DBP during BSL (cardiac cycle 6: BSL: 4.3 ± 3.2, DEX: 3.3 ± 2.0 mmHg; p = 0.025) and prolonged the time to peak DBP transduction (BSL: 6 ±1, DEX: 10 ± 3 cardiac cycles; p = 0.014). Also, DEX reduced DBP transduction gain (BSL: 1.6 ± 2.4, DEX: 0.9 ± 1.3 mmHg/cardiac cycle; p = 0.029). By contrast, DEX did not affect the mean transduction of MSNA bursts to changes in HR (BSL: 3.2 ± 3.1, DEX: 3.9 ± 4.6 mmHg; p = 0.668). These data suggest that α 2 -adrenergic mechanisms distributed among central and peripheral sympathetic neural regions and the cardiovascular system influence moment-to-moment sympathetic regulation of blood pressure homeostasis, but not HR, in humans. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This abstract was presented at the American Physiology Summit 2025 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.

Biological sex impacts baroreflex control of integrated muscle sympathetic nerve activity (MSNA), yet our knowledge remains incomplete regarding sex differences in baroreflex regulation of the differently sized APs contributing to variations in MSNA burst frequency and size. We hypothesized that sex differences in baroreflex control of sympathetic action potential (AP) discharge contribute to higher resting AP activity in males compared to females. We measured diastolic blood pressure (DBP; Finometer or brachial arterial catheter) and MSNA (peroneal microneurography and continuous wavelet transform, APs normalized to 10 clusters) in 24 healthy individuals (aged 18-30, 12 females) during a 5-minute supine baseline. Sympathetic AP baroreflex threshold gain was measured as the slope of the linear relationship between AP discharge probability and DBP. Sympathetic AP baroreflex sensitivity gain was measured as the slope of the linear relationship between AP clusters per burst and DBP. Analyses were performed during DBP rises and falls to explore baroreflex hysteresis. Mixed-effects analyses and t-tests were performed. Data are reported as mean ± SD. In the aggregate cohort, baroreflex control of medium-sized APs exhibited hysteresis. Compared to rises in DBP, DBP falls were associated with greater AP firing probabilities (cluster 3; DBP rise: 20 ± 11, DBP fall: 26 ± 12%; p < 0.01) and greater AP baroreflex gains (cluster 3; DBP rise: -4.36 ± 2.43, DBP fall: -5.32 ± 3.09 %/mmHg; p < 0.01). In the aggregate cohort, baroreflex hysteresis was not detected for small- or large-sized AP clusters (both p ≥ 0.56). Similar observations were detected for medium-sized APs in male (M) and female (F) cohorts when analyses were stratified by sex. Compared to females, males exhibited greater medium-sized AP firing probabilities during DBP rises (cluster 3; M: 23 ± 12, F: 16 ± 8%; p < 0.01) and falls (cluster 3; M: 32 ± 13, F: 20 ± 8%; p < 0.01). However, AP baroreflex gains were not different between sexes during DBP rises (cluster 3; M: -4.87 ± 2.05, F: -3.84 ± 2.75%/mmHg; p = 0.13) and falls (cluster 3; M: -5.87 ± 2.25, F: -4.76 ± 3.77 %/mmHg; p = 0.15). In the aggregate cohort, the number of AP clusters per burst and the AP baroreflex sensitivity gain were not different between rises and falls in DBP. However, compared to females, males demonstrated a greater number of AP clusters per burst during DBP rises (M: 4 ± 0.9, F: 3 ± 0.6 clusters/burst; p < 0.01) and falls (M: 4 ± 0.8, F: 3 ± 0.7 clusters/burst; p < 0.01). No sex differences in AP baroreflex sensitivity gain were detected during DBP rises (M: -0.08 ± 0.09, F: -0.30 ± 0.07 clusters/burst/mmHg; p = 0.14) or falls (M: -0.08 ± 0.08, F: -0.02 ± 0.08 clusters/burst/mmHg; p = 0.09). These data suggest that 1) hysteresis exists in baroreflex regulation of medium-sized but not small or large sympathetic APs firing under baseline conditions and 2) in line with earlier integrated MSNA studies, compared to females, males demonstrate greater resting sympathetic outflow from greater sympathetic AP discharge and more AP clusters firing per burst in periods of rising and falling DBPs. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This abstract was presented at the American Physiology Summit 2025 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.

The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.

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.