Sympathoinhibition during cardiopulmonary baroreceptor loading is attenuated in older females.

The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean ± SD, 70 ± 6 yr) and 11 younger females (20 ± 1 yr) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0°), and their lower limbs were passively lifted at 10°, 20°, 30°, and 40° (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females than in younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, -3.5 ± 1.5 vs. younger, -6.3 ± 1.5 bursts/min at 40° from baseline, P = 0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07 ± 0.37 vs. younger, +1.12 ± 0.33 mmHg at 40° from baseline, P = 0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females.NEW & NOTEWORTHY There were no available data concerning the effect of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. The magnitude of the decrease in muscle sympathetic nerve activity during passive leg raising (10°-40°) was smaller in older females than in young females. In females, inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age.

Aging in females has minimal effect on changes in celiac artery blood flow during dynamic light-intensity exercise.

Blood flow to the active muscles and arterial blood pressure (ABP) increase during dynamic exercise, whereas blood flow to inactive organs (e.g., splanchnic organs and inactive limbs) declines. Aging leads to exaggerated ABP responses to exercise in females, but whether this is related to greater splanchnic vasoconstriction is unknown. This study sought to clarify the effect of aging in females on celiac artery blood flow during dynamic light-intensity exercise. Twelve healthy young females (YF: 20 ± 2 yr, mean ± SD) and 12 healthy older females (OF: 71 ± 4 yr) performed dynamic knee-extension and knee-flexion exercises at 30% of heart rate reserve for 4 min. The absolute changes from baseline (Δ) for mean arterial blood pressure (MAP), celiac artery mean blood flow (celMBF), and celiac vascular conductance (celVC) during exercise were calculated. ABP was measured using an automated sphygmomanometer, and celMBF was recorded by Doppler ultrasonography. The increase in MAP during exercise was greater in OF than in YF (YF: +14 ± 7 mmHg, OF: +24 ± 13 mmHg, P = 0.028). The celMBF decreased during exercise in both groups, but there was no significant difference in the response between YF and OF (YF: -93.0 ± 66.1 mL/min, OF: -89.6 ± 64.0 mL/min, P = 0.951). The celVC also decreased during exercise and remained lower than baseline during exercise. However, the response was not different between YF and OF (YF: -1.8 ± 1.0 mL/min/mmHg, OF: -1.5 ± 0.6 mL/min/mmHg, P = 0.517). These results demonstrate that aging in females has minimal influence on splanchnic artery hemodynamic responses during dynamic light-intensity exercise, suggesting that exaggerated ABP responses during exercise in OF are not due to greater splanchnic vasoconstriction.NEW & NOTEWORTHY During exercise, the splanchnic arteries vasoconstrict, contributing to blood flow redistribution and the blood pressure response. Blood pressure responses to exercise are exaggerated with aging in females; however, the physiological mechanism responsible has not been clarified. We show that celiac artery blood flow changes during light-intensity dynamic exercise do not differ with age in females. This indicates the exaggerated blood pressure to exercise with aging is likely not due to a difference in splanchnic vasoconstriction.

Assessing functional sympatholysis during rhythmic handgrip exercise using Doppler ultrasound and near-infrared spectroscopy: sex differences and test-retest reliability.

The effects of sympathetic activity on vasoconstriction are dampened in active skeletal muscle during exercise, a phenomenon termed functional sympatholysis. Limited work has examined the influence of sex on the magnitude of sympatholysis or the test-retest reliability of measurements. In 16 women and 15 men, forearm blood flow (FBF; Doppler ultrasound), muscle oxygenation (near-infrared spectroscopy, NIRS), and beat-to-beat mean arterial pressure (MAP; photoplethysmography) were measured during lower-body negative pressure (LBNP; -20 mmHg) at rest and simultaneously during rhythmic handgrip exercise (30% maximum contraction). Measures were taken twice within the same visit (separated by 15 min) and repeated on a second visit. Forearm vascular conductance (FVC) was calculated as FBF/MAP. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes between handgrip and rest. LBNP decreased FBF (Δ-45 ± 15%), FVC (Δ-45 ± 16%), and muscle oxygenation (Δ-14 ± 11%); however, these responses were attenuated when LBNP was applied during rhythmic handgrip exercise (Δ-7 ± 9%, Δ-9 ± 10%, and Δ-6 ± 9%, respectively). The magnitude of sympatholysis was not different between men and women (FBF: 40 ± 16% vs. 35 ± 9%, P = 0.37; FVC: 38 ± 16% vs. 35 ± 11%, P = 0.53; muscle oxygenation: 5 ± 9% vs. 11 ± 10%, P = 0.11). Furthermore, sympatholysis measurements demonstrated good to excellent intraday (intraclass-correlation coefficients; ICC ≥ 0.85) and interday (ICC ≥ 0.72) test-retest reliability (all P ≤ 0.01) in both sexes. The coefficients of variation were larger with NIRS (68-91%) than with Doppler ultrasound (16%-22%) assessments of functional sympatholysis. Collectively, these findings demonstrate that assessments of functional sympatholysis are not impacted by biological sex and that Doppler ultrasound-derived measures of sympatholysis have better within-subject reliability than NIRS-derived measures in young healthy adults.

Sympathetic transduction of blood pressure during graded lower body negative pressure in young healthy adults.

Sympathetic transduction of blood pressure (BP) is correlated negatively with resting muscle sympathetic nerve activity (MSNA) in cross-sectional data, but the acute effects of increasing MSNA are unclear. Sixteen (4 female) healthy adults (26 ± 3 years) underwent continuous measurement of heart rate, BP, and MSNA at rest and during graded lower body negative pressure (LBNP) at -10, -20, and -30 mmHg. Sympathetic transduction of BP was quantified in the time (signal averaging) and frequency (MSNA-BP gain) domains. The proportions of MSNA bursts firing within each tertile of BP were calculated. As expected, LBNP increased MSNA burst frequency (P < 0.01) and burst amplitude (P < 0.02), although the proportions of MSNA bursts firing across each BP tertile remained stable (all P > 0.44). The MSNA-diastolic BP low-frequency transfer function gain (P = 0.25) was unchanged during LBNP; the spectral coherence was increased (P = 0.03). Signal-averaged sympathetic transduction of diastolic BP was unchanged (from 2.1 ± 1.0 at rest to 2.4 ± 1.5, 2.2 ± 1.3, and 2.3 ± 1.4 mmHg; P = 0.43) during LBNP, but diastolic BP responses following nonburst cardiac cycles progressively decreased (from -0.8 ± 0.4 at rest to -1.0 ± 0.6, -1.2 ± 0.6, and -1.6 ± 0.9 mmHg; P < 0.01). As a result, the difference between MSNA burst and nonburst diastolic BP responses was increased (from 2.9 ± 1.4 at rest to 3.4 ± 1.9, 3.4 ± 1.9, and 3.9 ± 2.1 mmHg; P < 0.01). In conclusion, acute increases in MSNA using LBNP did not alter traditional signal-averaged or frequency-domain measures of sympathetic transduction of BP or the proportion of MSNA bursts firing at different BP levels. The factors that determine changes in the firing of MSNA bursts relative to oscillations in BP require further investigation.

Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency?

Calculating the blood pressure (BP) response to a burst of muscle sympathetic nerve activity (MSNA), termed sympathetic transduction, may be influenced by an individual's resting burst frequency. We examined the relationships between sympathetic transduction and MSNA in 107 healthy males and females and developed a normalized sympathetic transduction metric to incorporate resting MSNA. Burst-triggered signal averaging was used to calculate the peak diastolic BP response following each MSNA burst (sympathetic transduction of BP) and following incorporation of MSNA burst cluster patterns and amplitudes (sympathetic transduction slope). MSNA burst frequency was negatively correlated with sympathetic transduction of BP (r = -0.42; P < 0.01) and the sympathetic transduction slope (r = -0.66; P < 0.01), independent of sex. MSNA burst amplitude was unrelated to sympathetic transduction of BP in males (r = 0.04; P = 0.78), but positively correlated in females (r = 0.44; P < 0.01) and with the sympathetic transduction slope in all participants (r = 0.42; P < 0.01). To control for MSNA, the linear regression slope of the log-log relationship between sympathetic transduction and MSNA burst frequency was used as a correction exponent. In subanalysis of males (38 ± 10 vs. 14 ± 4 bursts/min) and females (28 ± 5 vs. 12 ± 4 bursts/min) with high versus low MSNA, sympathetic transduction of BP and sympathetic transduction slope were lower in participants with high MSNA (all P < 0.05). In contrast, normalized sympathetic transduction of BP and normalized sympathetic transduction slope were similar in males and females with high versus low MSNA (all P > 0.22). We propose that incorporating MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.

Muscle sympathetic single-unit response patterns during progressive muscle metaboreflex activation in young healthy adults.

Muscle sympathetic single units can respond differentially to stress, but whether these responses are linked to the degree of sympathoexcitation is unclear. Fifty-three muscle sympathetic single units (microneurography) were recorded in 17 participants (8 women; 24 ± 3 yr). Five 40-s bouts of 10% static handgrip were performed during a 10-min forearm ischemia to progressively increase metabolite accumulation. Each static handgrip was separated by a 75-s ischemic rest [postexercise circulatory occlusion (PECO)] to assess the isolated action of the muscle metaboreflex. During each set of PECO, individual single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. From sets 1-5 of PECO, the proportion of single units with activated (34, 45, 68, 87, and 89%), nonresponsive (43, 44, 23, 7, and 9%), or inhibited (23, 11, 9, 6, and 2%) responses changed (P < 0.001) as total muscle sympathoexcitation increased. A total of 51/53 (96%) single units were activated in at least one set of PECO, 16 (31%) initially inhibited before activation. This response pattern delayed the activation onset compared with noninhibited units (set 3 ± 1 vs. 2 ± 1, P < 0.001). Once activated, the spike-frequency rate of rise was similar (8.5 ± 6.5 vs. 7.1 ± 6.0 spikes/min per set, P = 0.48). Muscle sympathetic single-unit firing demonstrated differential control during muscle metaboreflex activation. Single units that were initially inhibited during progressive metaboreflex activation were capable of being activated in later sets. These findings reveal that single-unit activity is influenced by convergent neural inputs (i.e., both inhibitory and excitatory), which yield heterogenous single-unit activation thresholds.NEW & NOTEWORTHY Muscle sympathetic single units respond differentially to sympathoexcitatory stress such that single units can increase firing to contribute to the sympathoexcitatory response or can be nonresponsive or even inhibited. We observed a subgroup of single units that can respond bidirectionally, being first inhibited before activated by progressive increases in forearm muscle metaboreflex activation. These results suggest convergent neural inputs (i.e., inhibitory and excitatory), which yield heterogenous muscle sympathetic single-unit activation thresholds.

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.

Evidence for differential control of muscle sympathetic single units during mild sympathoexcitation in young, healthy humans.

Two subpopulations of muscle sympathetic single units with opposite discharge characteristics have been identified during low-level cardiopulmonary baroreflex loading and unloading in middle-aged adults and patients with heart failure. The present study sought to determine whether similar subpopulations are present in young healthy adults during cardiopulmonary baroreflex unloading ( study 1) and rhythmic handgrip exercise ( study 2). Continuous hemodynamic and multiunit and single unit muscle sympathetic nerve activity (MSNA) data were collected at baseline and during nonhypotensive lower body negative pressure (LBNP; n = 12) and 40% maximal voluntary contraction rhythmic handgrip exercise (RHG; n = 24). Single unit MSNA responses were classified as anticipated or paradoxical based on whether changes were concordant or discordant with the multiunit MSNA response, respectively. LBNP and RHG both increased multiunit MSNA burst frequency (∆5 ± 3 bursts/min, P < 0.001; ∆5 ± 8 bursts/min, P = 0.005), burst amplitude (∆5 ± 7%, P = 0.04; ∆13 ± 14%, P < 0.001), and total MSNA (∆302 ± 191 AU/min, P = 0.001; ∆585 ± 556 AU/min, P < 0.001). During LBNP and RHG, 43 and 64 muscle single units were identified, respectively, which increased spike frequency (∆9 ± 11 spikes/min, P < 0.001; ∆10 ± 19 spikes/min, P < 0.001) and the probability of multiple spike firing (∆10 ± 12%, P < 0.001; ∆11 ± 26%, P = 0.001). During LBNP and RHG, 36 (84%) and 39 (61%) single units possessed anticipated firing responses (∆12 ± 10 spikes/min, P < 0.001; ∆19 ± 19 spikes/min, P < 0.001), whereas 7 (16%) and 25 (39%) single units exhibited paradoxical reductions (∆-3 ± 1 spikes/min, P = 0.003; ∆-4 ± 5 spikes/min, P < 0.001). The observation of divergent subpopulations of muscle sympathetic single units in healthy young humans during two mild sympathoexcitatory stressors supports differential control at the fiber level as a fundamental characteristic of human sympathetic regulation. NEW & NOTEWORTHY The activity of muscle sympathetic single units was recorded during cardiopulmonary baroreceptor unloading and rhythmic handgrip exercise in young healthy humans. During both stressors, the majority of single units (84% and 61%) exhibited anticipated behavior concordant with the integrated muscle sympathetic response, whereas a smaller proportion (16% and 39%) exhibited paradoxical sympathoinhibition. These results support differential control of postganglionic muscle sympathetic fibers as a characteristic of human sympathetic regulation during mild sympathoexcitatory stress. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/differential-control-of-sympathetic-outflow-in-young-humans/ .

Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared with eicosapentaenoic acid in healthy men and women.

Supplementation with monounsaturated or ω-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ω-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [-3.4 mmHg (-0.9, -5.9), P = 0.008] and OO [-3.0 mmHg (-0.5, -5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [-3.4 mmHg (-1.3,-5.6), P = 0.002] and OO [-2.2 mmHg (0.08,-4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (-0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [-3 bursts/min (-6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.

TRPV1 and BDKRB2 receptor polymorphisms can influence the exercise pressor reflex.

KEY POINTS: The mechanisms responsible for the high inter-individual variability in blood pressure responses to exercise remain unclear. Common genetic variants of genes related to the vascular transduction of sympathetic outflow have been investigated, but variants influencing skeletal muscle afferent feedback during exercise have not been explored. Single nucleotide polymorphisms in TRPV1 rs222747 and BDKRB2 rs1799722 receptors present in skeletal muscle were associated with differences in the magnitude of the blood pressure response to static handgrip exercise but not mental stress. The combined effects of TRPV1 rs222747 and BDKRB2 rs1799722 on blood pressure and heart rate responses during exercise were additive, and primarily found in men. Genetic differences in skeletal muscle metaboreceptors may be a risk factor for exaggerated blood pressure responses to exercise. ABSTRACT: Exercise blood pressure (BP) responses demonstrate high inter-individual variability, which could relate to differences in metabolically sensitive afferent feedback from the exercising muscle. We hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding metaboreceptors present in group III/IV skeletal muscle afferents can influence the exercise pressor response. Two hundred men and women underwent measurements of continuous BP and heart rate at baseline and during 2 min of static handgrip exercise (30% maximal volitional contraction), post-exercise circulatory occlusion and mental stress (serial subtraction; internal control). Participants were genotyped for SNPs in TRPV1 (rs222747; G/C), ASIC3 (rs2288645; G/A), BDKRB2 (rs1799722; C/T), PTGER2 (rs17197; A/G) and P2RX4 (rs25644; A/G). Exercise systolic BP (19 ± 10 vs. 22 ± 10 mmHg, P = 0.03) was lower in GG versus GC/CC minor allele carriers for TRPV1 rs222747, while exercise diastolic BP (14 ± 7 vs. 17 ± 7 mmHg, P = 0.007) and heart rate (12 ± 8 vs. 15 ± 9 beats min-1 , P = 0.03) were lower in CC versus CT/TT minor allele carriers for BDKRB2 rs1799722. Individuals carrying both minor alleles for TRPV1 rs222747 and BDKRB2 rs1799722 had greater systolic (22 ± 11 vs. 17 ± 10 mmHg, P = 0.04) and diastolic (18 ± 7 vs. 14 ± 7 mmHg, P = 0.01) BP responses than those with no minor alleles; these differences were larger in men. No differences in BP or heart rate responses were detected during static handgrip with ASIC3 rs2288645, PTGER2 rs17197 or P2RX4 rs25644. None of the selected SNPs were associated with differences during mental stress. These findings demonstrate that variants in TRPV1 and BDKRB2 receptors can contribute to BP differences during static exercise in an additive manner.

Interindividual variability in muscle sympathetic responses to static handgrip in young men: evidence for sympathetic responder types?

Negative and positive muscle sympathetic nerve activity (MSNA) responders have been observed during mental stress. We hypothesized that similar MSNA response patterns could be identified during the first minute of static handgrip and contribute to the interindividual variability throughout exercise. Supine measurements of multiunit MSNA (microneurography) and continuous blood pressure (Finometer) were recorded in 29 young healthy men during the first (HG1) and second (HG2) minute of static handgrip (30% maximal voluntary contraction) and subsequent postexercise circulatory occlusion (PECO). Responders were identified on the basis of differences from the typical error of baseline total MSNA: 7 negative, 12 positive, and 10 nonresponse patterns. Positive responders demonstrated larger total MSNA responses during HG1 ( P < 0.01) and HG2 ( P < 0.0001); however, the increases in blood pressure throughout handgrip exercise were similar between all groups, as were the changes in heart rate, stroke volume, cardiac output, total vascular conductance, and respiration (all P > 0.05). Comparing negative and positive responders, total MSNA responses were similar during PECO ( P = 0.17) but opposite from HG2 to PECO (∆40 ± 46 vs. ∆-21 ± 62%, P = 0.04). Negative responders also had a shorter time-to-peak diastolic blood pressure during HG1 (20 ± 20 vs. 44 ± 14 s, P < 0.001). Total MSNA responses during HG1 were associated with responses to PECO ( r = 0.39, P < 0.05), the change from HG2 to PECO ( r = -0.49, P < 0.01), and diastolic blood pressure time to peak ( r = 0.50, P < 0.01). Overall, MSNA response patterns during the first minute of static handgrip contribute to interindividual variability and appear to be influenced by differences in central command, muscle metaboreflex activation, and rate of loading of the arterial baroreflex.

Influence of sex on sympathetic vasomotor outflow responses to passive leg raising in young individuals.

The purpose of this study was to clarify sex differences in the inhibition of sympathetic vasomotor outflow which is caused by the loading of cardiopulmonary baroreceptors. Ten young males and ten age-matched females participated. The participants underwent a passive leg raising (PLR) test wherein they were positioned supine (baseline, 0º), and their lower limbs were lifted passively at 10º, 20º, 30º, and 40º. Each angle lasted for 3 min. Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. Baseline MSNA was lower in females compared to males. MSNA burst frequency was decreased during the PLR in both males (- 6.2 ± 0.4 bursts/min at 40º) and females (- 6.5 ± 0.4 bursts/min at 40º), but no significant difference was detected between the two groups (P = 0.61). These results suggest that sex has minimal influence on the inhibition of sympathetic vasomotor outflow during the loading of cardiopulmonary baroreceptors in young individuals.

Renal vascular conductance is unrelated to leg vascular conductance or muscle sympathetic nerve activity at rest and during stress in humans.

The sympathetic nervous system is important for cardiovascular regulation, particularly during acute stress. Efferent sympathetic outflow can be regulated in an organ-dependent manner, but whether renal and leg vasoconstriction are associated at rest or during sympathetic stressors is unknown. Therefore, we sought to determine the relationships between muscle sympathetic nerve activity (MSNA), leg vascular conductance (LVC), and renal vascular conductance (RVC) at rest and during common laboratory-based sympathoexcitatory stimuli in a cohort of young healthy adults. Beat-to-beat arterial pressure (photoplethysmography), MSNA (microneurography), superficial femoral artery blood flow, and renal artery blood velocity (Doppler ultrasound) were measured at rest and during static handgrip exercise (30% maximal voluntary contraction), postexercise circulatory occlusion (PECO), and cold stress (hand in 3.8 ± 1.3°C water) in 37 young healthy adults (16 females, 21 males). At rest, RVC was unrelated to LVC (r = -0.11, P = 0.55) or MSNA burst frequency (ρ = -0.22, P = 0.26). Static handgrip, PECO, and cold stress each induced an increase in mean arterial pressure and MSNA and a reduction in RVC (all P < 0.001). LVC was unaltered during stress (all P ≥ 0.16), with the exception of a reduction during the second minute of cold stress (P = 0.03). During stress, changes in RVC were not associated with changes in LVC (handgrip: r = -0.24, P = 0.21; PECO: ρ = -0.04, P = 0.82; cold stress: r = -0.17, P = 0.38) or MSNA (handgrip: ρ = -0.14, P = 0.48; PECO: r = 0.27, P = 0.15; cold stress: r = -0.27, P = 0.16). Furthermore, MSNA was not associated with LVC at rest or during stress (all P ≥ 0.12). The present findings highlight the differential control of regional sympathetic vasoconstriction at rest and during stress in young healthy humans.NEW & NOTEWORTHY The sympathetic nervous system plays a critical role in cardiovascular regulation at rest and during stress. We demonstrate that renal artery vascular conductance is unrelated to superficial femoral artery vascular conductance or muscle sympathetic nerve activity at rest or during laboratory-based sympathetic stressors in young healthy adults. These findings support the concept of differential control of peripheral sympathetic outflow at rest and during stress in humans.

Blood Pressure Responses to Postexercise Circulatory Occlusion Are Attenuated After Exercise-Induced Muscle Weakness.

PURPOSE: Exercise blood pressure (BP) responses are thought to be determined by relative exercise intensity (percent maximal voluntary contraction (MVC) strength). However, cross-sectional studies report that during a static contraction, higher absolute force is associated with greater BP responses to relative intensity exercise and subsequent muscle metaboreflex activation with postexercise circulatory occlusion (PECO). We hypothesized that a bout of unaccustomed eccentric exercise would reduce knee extensor MVC and subsequently attenuate BP responses to PECO. METHODS: Continuous BP, heart rate, muscle oxygenation, and knee extensor electromyography were recorded in 21 young healthy individuals (female, n = 10) during 2 min of 20% MVC static knee extension exercise and 2 min of PECO, performed before and 24 h after 300 maximal knee extensor eccentric contractions to cause exercise-induced muscle weakness. As a control, 14 participants repeated the eccentric exercise 4 wks later to test whether BP responses were altered when exercise-induced muscle weakness was attenuated via the protective effects of the repeated bout effect. RESULTS: Eccentric exercise reduced MVC in all participants (144 ± 43 vs 110 ± 34 N·m, P < 0.0001). BP responses to matched relative intensity static exercise (lower absolute force) were unchanged after eccentric exercise ( P > 0.99) but were attenuated during PECO (systolic BP: 18 ± 10 vs 12 ± 9 mm Hg, P = 0.02). Exercise-induced muscle weakness modulated the deoxygenated hemoglobin response to static exercise (64% ± 22% vs 46% ± 22%, P = 0.04). When repeated after 4 wks, exercise-induced weakness after eccentric exercise was attenuated (-21.6% ± 14.3% vs -9.3 ± 9.7, P = 0.0002) and BP responses to PECO were not different from control values (all, P > 0.96). CONCLUSIONS: BP responses to muscle metaboreflex activation, but not exercise, are attenuated by exercise-induced muscle weakness, indicating a contribution of absolute exercise intensity on muscle metaboreflex activation.

Cardiovascular responses to combined mechanoreflex and metaboreflex activation in healthy adults: effects of sex and low- versus high-hormone phases in females.

Females generally have smaller blood pressure (BP) responses to isolated muscle mechanoreflex and metaboreflex activation compared with males, which may explain sex differences in BP responses to voluntary exercise. The mechanoreflex may be sensitized during exercise, but whether mechanoreflex-metaboreflex interactions differ by sex or variations in sex hormones remains unknown. Thirty-one young healthy subjects (females, n = 16) performed unilateral passive cycling (mechanoreflex), active cycling (40% peak Watts), postexercise circulatory occlusion (PECO; metaboreflex), and passive cycling combined with PECO (combined mechanoreflex and metaboreflex activation). Beat-to-beat BP, heart rate, inactive leg vascular conductance, and active leg muscle oxygenation were measured. Ten females underwent exploratory testing during low- and high-hormone phases of their self-reported menstrual cycle or oral contraceptive use. Systolic BP and heart rate responses did not differ between sexes during active cycling [Δ30 ± 9 vs. 29 ± 11 mmHg (males vs. females), P = 0.9; Δ33 ± 8 vs. 35 ± 6 beats/min, P = 0.4] or passive cycling with PECO (Δ26 ± 11 vs. 21 ± 10 mmHg, P = 0.3; Δ14 ± 7 vs. 18 ± 15 beats/min, P = 0.3). Passive cycling with PECO revealed additive, not synergistic, effects for systolic BP [males: Δ23 ± 14 vs. 26 ± 11 mmHg (sum of isolated passive cycling and PECO vs. combined activation); females: Δ26 ± 11 vs. 21 ± 12 mmHg, interaction P = 0.05]. Results were consistent in subset analyses with sex differences in active cycling BP (P > 0.1) and exploratory analyses of hormone phase (P > 0.4). Despite a lack of statistical equivalence, no differences in cardiovascular responses were found during combined mechanoreflex-metaboreflex activation between sexes or hormone levels. These results provide preliminary data regarding the involvement of muscle mechanoreflex-metaboreflex interactions in mediating sex differences in voluntary exercise BP responses.NEW & NOTEWORTHY The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.

Effects of sex and menstrual cycle phase on celiac artery blood flow during dynamic moderate-intensity leg exercise in young individuals.

The purpose of this study was to clarify the effect of sex and menstrual cycle phase on celiac artery blood flow during dynamic exercise in healthy young humans. Eleven healthy young females (21 ± 2 yr, means ± SD) and 10 males (23 ± 3 yr) performed dynamic knee-extension and -flexion exercises at 30% of heart rate reserve for 4 min. The percent changes from baseline (Δ) for mean arterial blood pressure (MAP), mean blood flow (celMBF) in the celiac artery, and celiac vascular conductance (celVC) during exercise were calculated. Arterial blood pressure was measured using an automated sphygmomanometer, and celiac artery blood flow was recorded by Doppler ultrasonography. Female subjects performed the exercise test in the early follicular phase (EF) and in the midluteal phase (ML) of their menstrual cycle. The increase in MAP during exercise was not significantly (P > 0.05) different between sexes or between menstrual cycle phases (ΔMAP, EF in females: +16.6 ± 6.4%, ML in females: +20.2 ± 11.7%, and males: +19.9 ± 12.2%). The celMBF decreased during exercise in each group, but the response was not significantly (P > 0.05) different between sexes or between menstrual cycle phases (ΔcelMBF, EF in females: -24.6 ± 15.5%, ML in females: -25.2 ± 18.7%, and males: -29.2 ± 4.0%). The celVC decreased during dynamic exercise in each group, with no significant (P > 0.05) difference in the responses between sexes or between menstrual cycle phases (ΔcelVC, EF in females: -38.3 ± 15.0%, ML in females: -41.5 ± 19.1%, and males: -43.4 ± 7.2%). These results suggest that sex and menstrual cycle phase have minimal influence on hemodynamic responses in the splanchnic artery during dynamic moderate-intensity exercise in young healthy individuals.NEW & NOTEWORTHY During dynamic exercise, splanchnic organ blood flow is reduced from resting values. Whether sex and menstrual cycle phase influence splanchnic blood flow responses during exercise remains unknown. We show that the decrease in celiac artery blood flow during dynamic leg exercise does not differ between young females and males or between menstrual cycle phases. In young individuals, sex and menstrual cycle have minimal influence on splanchnic artery hemodynamic responses during dynamic moderate-intensity leg exercise.