Effects of muscle sympathetic burst size and burst pattern on time-to-peak sympathetic transduction.

The current study evaluated the influence of resting muscle sympathetic nerve activity (MSNA) burst size and firing pattern on time-to-peak sympathetic transduction in 36 young healthy men and women. Participants underwent a 5-10 min resting baseline with beat-to-beat measures of heart rate, mean arterial pressure (MAP), and MSNA (microneurography). Cardiac output and total vascular conductance were calculated using the Modelflow algorithm. Sympathetic transduction was quantified using the burst-triggered signal averaging technique to examine the changes in MAP, cardiac output, and total vascular conductance for 15 cardiac cycles after each MSNA burst or non-burst. A stepwise increase in the peak MAP (i.e., sympathetic transduction) was observed throughout all quartiles of normalized MSNA burst area (quartile 1 (Q1): 1.7 ± 1.3 mm Hg; Q2: 2.1 ± 1.3 mm Hg; Q3: 2.6 ± 1.4 mm Hg; Q4: 3.5 ± 1.4 mm Hg; P < 0.01). The largest quartile of normalized MSNA burst area demonstrated faster time-to-peak MAP responses (5.7 ± 2.5 s) than both Q1 (10.1 ± 3.9 s, P < 0.01) and Q2 (9.3 ± 4.1 s, P < 0.01), as well as, faster time-to-peak cardiac output and time-to-nadir total vascular conductance compared with Q1 and Q2 (All P < 0.05). Larger clusters of sympathetic bursts (i.e., triplets and ≥ quadruplets) did not have increased time-to-peak transduction compared with singlets and doublet bursts across all MSNA quartiles. These results highlight intraindividual variability in the time-course of sympathetic transduction and reveal an intrinsic property of larger sympathetic bursts to increase time-to-peak sympathetic transduction in humans. Novelty: Muscle sympathetic burst size can modulate time-to-peak sympathetic transduction in young healthy men and women. These observations appear independent of the pattern of sympathetic firing.

Arterial baroreflex regulation of muscle sympathetic nerve activity at rest and during stress.

KEY POINTS: The arterial baroreflex controls vasoconstrictor muscle sympathetic nerve activity (MSNA) in a negative feedback manner by increasing or decreasing activity during spontaneous blood pressure falls or elevations, respectively. Spontaneous sympathetic baroreflex sensitivity is commonly quantified as the slope of the relationship between MSNA burst incidence or strength and beat-to-beat variations in absolute diastolic blood pressure. We assessed the relationships between blood pressure inputs related to beat-to-beat blood pressure change or blood pressure rate-of-change (variables largely independent of absolute pressure) and MSNA at rest and during exercise and mental stress. The number of participants with strong linear relationships between MSNA and beat-to-beat diastolic blood pressure change variables or absolute diastolic blood pressure were similar at rest, although during stress the beat-to-beat diastolic blood pressure change variables were superior. Current methods may not fully characterize the capacity of the arterial baroreflex to regulate MSNA. ABSTRACT: Spontaneous sympathetic baroreflex sensitivity (sBRS) is commonly quantified as the slope of the relationship between variations in absolute diastolic blood pressure (DBP) and muscle sympathetic nerve activity (MSNA) burst incidence or strength. This relationship is well maintained at rest but not during stress. We assessed whether sBRS could be calculated at rest and during stress (static handgrip, rhythmic handgrip, mental stress) using blood pressure variables that quantify relative change: beat-to-beat DBP change (ΔDBP), ΔDBP rate-of-change (ΔDBP rate), pulse pressure (PP) and PP rate-of-change (PP rate). Sixty-six healthy participants underwent continuous measures of blood pressure (finger photoplethysmography) and multi-unit MSNA (microneurography). At rest, absolute DBP (91%), ΔDBP (97%) and ΔDBP rate (97%) each yielded higher proportions of participants with strong linear relationships (r ≥ 0.6) with MSNA burst incidence compared to PP (57%) and PP rate (56%) and produced similar sBRS slopes (DBP: -4.5 ± 2.0 bursts 100 heartbeats-1 /mmHg; ΔDBP: -5.0 ± 2.1 bursts 100 heartbeats-1 /ΔmmHg; ΔDBP rate: -4.9 ± 2.2 bursts 100 heartbeats-1 /ΔmmHg s-1 ; P > 0.05). During stress, ΔDBP (74%) and ΔDBP rate (74%) yielded higher proportions of strong linear relationships with MSNA burst incidence than absolute DBP (43%), PP (46%) and PP rate (49%) (all P < 0.05). The absolute DBP associated with a 50% chance of a MSNA burst (T50 ) was shifted rightward during static handgrip (Δ+15 ± 11 mmHg, P < 0.001) and mental stress (Δ+11 ± 7 mmHg, P < 0.001); however, the ΔDBP T50 was shifted rightward during static handgrip (Δ+2.5 ± 3.7 mmHg, P = 0.009) but not mental stress (Δ0.0 ± 4.4 mmHg, P = 0.99). These findings suggest that calculating sBRS using absolute DBP alone may not adequately characterize arterial baroreflex regulation of MSNA, particularly during stress.

Effects of dynamic arm and leg exercise on muscle sympathetic nerve activity and vascular conductance in the inactive leg.

The influence of muscle sympathetic nerve activity (MSNA) responses on local vascular conductance during exercise are not well established. Variations in exercise mode and active muscle mass can produce divergent MSNA responses. Therefore, we sought to examine the effects of small- versus large-muscle mass dynamic exercise on vascular conductance and MSNA responses in the inactive limb. Thirty-five participants completed two study visits in a randomized order. During visit 1, superficial femoral artery (SFA) blood flow (Doppler ultrasound) was assessed at rest and during steady-state rhythmic handgrip (RHG; 1:1 duty cycle, 40% maximal voluntary contraction), one-leg cycling (17 ± 3% peak power output), and concurrent exercise at the same intensities. During visit 2, MSNA (contralateral fibular nerve microneurography) was acquired successfully in 12/35 participants during the same exercise modes. SFA blood flow increased during RHG (P < 0.0001) and concurrent exercise (P = 0.03) but not cycling (P = 0.91). SFA vascular conductance was unchanged during RHG (P = 0.88) but reduced similarly during concurrent and cycling exercise (both P < 0.003). RHG increased MSNA burst frequency (P = 0.04) without altering burst amplitude (P = 0.69) or total MSNA (P = 0.26). In contrast, cycling and concurrent exercise had no effects on MSNA burst frequency (both P ≥ 0.10) but increased burst amplitude (both P ≤ 0.001) and total MSNA (both P ≤ 0.007). Across all exercise modes, the changes in MSNA burst amplitude and SFA vascular conductance were correlated negatively (r = -0.43, P = 0.02). In summary, the functional vascular consequences of alterations in sympathetic outflow to skeletal muscle are most closely associated with changes in MSNA burst amplitude, but not frequency, during low-intensity dynamic exercise.NEW & NOTEWORTHY Low-intensity small- versus large-muscle mass exercise can elicit divergent effects on muscle sympathetic nerve activity (MSNA). We examined the relationships between changes in MSNA (burst frequency and amplitude) and superficial femoral artery (SFA) vascular conductance during rhythmic handgrip, one-leg cycling, and concurrent exercise in the inactive leg. Only changes in MSNA burst amplitude were inversely associated with SFA vascular conductance responses. This result highlights the functional importance of measuring MSNA burst amplitude during exercise.