Abstract P103: Aberrant Sympathetic Neural Recruitment Strategies During Exercise Pressor Reflex Activation In Postmenopausal Women

Age-related elevations in sympathetic nerve activity contribute to numerous deleterious consequences for cardiovascular health, particularly in postmenopausal women (PMW). Aging adversely affects aspects of sympathetic nervous system (SNS) coding to control blood pressure at rest and during physiological stress. Although PMW exhibit greater neural activity at rest, the underlying sympathetic discharge patterns, particularly during sympathoexcitation, remain unknown. This study aimed to test the hypothesis that PMW display aberrant neural coding strategies during physiological stress compared to young women (YW). Efferent muscle sympathetic nerve activity (microneurography) was measured at baseline and during the final minute of both 30% isometric handgrip (HG) and post-exercise ischemia (PEI) in five healthy YW (22 ± 2 y, 20 ± 4 kg/m 2 , mean blood pressure: 82 ± 7 mmHg) and five healthy PMW (60 ± 5 y, 23 ± 3 kg/m 2 , 87 ± 8 mmHg). Sympathetic action potential (AP) discharge patterns were examined using wavelet-based methodology. At baseline, PMW exhibited elevated integrated burst frequency (PMW 30 ± 10 vs YW 9 ± 3 bursts/min; p < 0.01) and increased AP firing (PMW 240 ± 117 vs YW 90 ± 64 APs/min, p = 0.04). Both groups had similar increases in integrated burst frequency during HG and PEI (p < 0.01 vs baseline). AP firing was elevated to a similar extent in both groups during HG (PMW Δ76 ± 60; YW Δ129 ± 146 APs/min; p < 0.01 vs baseline) and PEI (PMW Δ72 ± 51; YW Δ93 ± 64 APs/min; p < 0.01 vs baseline), with no change in the mean AP content per burst (p = 0.86). PMW had reduced recruitment of latent and larger AP subpopulations that were previously silent at baseline (group-by-condition interaction: p < 0.01), as evidenced by an increase in total AP clusters (binned according to peak-to-peak amplitude) during HG and PEI in YW (HG: Δ2 ± 1; PEI: Δ2 ± 2; both p ≤ 0.03 vs baseline) but not PMW (HG: Δ0 ± 1; PEI: Δ0 ± 1; both p ≥ 0.75 vs baseline). These preliminary data suggest that PMW display elevated resting sympathetic AP firing and aberrant reflex AP recruitment, such that the ability of the SNS to recruit subpopulations of previously silent axons during a sympathetic stressor is reduced in PWM compared to YW. These findings extend our knowledge of age-related neural coding strategies in women.

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Influence of Sex and Age on Muscle Sympathetic Nerve Activity of Healthy Normotensive Adults

Hypertension ◽

10.1161/hypertensionaha.120.15208 ◽

2020 ◽

Vol 76 (3) ◽

pp. 997-1005 ◽

Cited By ~ 5

Author(s):

Daniel A. Keir ◽

Mark B. Badrov ◽

George Tomlinson ◽

Catherine F. Notarius ◽

Derek S. Kimmerly ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Body Mass ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Systematic Change ◽

Burst Frequency ◽

Nerve Activity ◽

Age Related

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18–78 years [mean±SD]) and 260 female (age: 37±18; range: 18–81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min −1 ; P <1×10 −19 ; 106±11/66±8 versus 116±7/68±9 mm Hg; P <0.01) but converged thereafter (38±11 versus 35±12 bursts·min −1 ; P =0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P >0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, −4 to 5) and 12 (95% CI, 6–16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women.

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Abstract 125: Elevated Muscle Sympathetic Nerve Activity is Associated With Higher Aortic and Carotid Stiffness Independent of Blood Pressure in Women

Hypertension ◽

10.1161/hyp.70.suppl_1.125 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Seth W Holwerda ◽

Rachel E Luehrs ◽

Nealy A Wooldridge ◽

Lyndsey E DuBose ◽

Jess G Fiedorowicz ◽

...

Keyword(s):

Blood Pressure ◽

Arterial Stiffness ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Strongly Correlated ◽

Nerve Activity ◽

Arterial Blood ◽

Age Related ◽

Related Increase

Central arterial stiffness, a significant contributor to the development of hypertension and cardiovascular disease with aging, is linked to elevated muscle sympathetic nerve activity (MSNA) in men. However, the extent to which MSNA is associated with central arterial stiffness in women is unknown. Given that the age-related increase in MSNA and arterial blood pressure (BP) occurs at a steeper rate among women compared to men, we tested the hypothesis that resting MSNA is more strongly correlated with central arterial stiffness in women than in men. Also, because of the parallel age-related increase in MSNA, we further hypothesized that the relation between MSNA and central arterial stiffness would not be independent of age. MSNA (microneurography), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), and carotid β-stiffness (carotid tonometry and ultrasound) were assessed in 54 healthy men (n=29; 19-72 yrs; 30 ± 1 kg/m 2 ; systolic BP: 128 ± 3 mmHg) and women (n=26; 26-64 yrs; 29 ± 2 kg/m 2 ; systolic BP: 116 ± 3 mmHg). No differences between men and women were observed for CFPWV (Men: 7.0 ± 0.3 vs. Women: 6.8 ± 0.4 mmHg, P=0.747) and carotid β-stiffness (Men: 7.6 ± 0.8 vs. Women: 7.6 ± 0.5 mmHg, P=0.975). Mean BP was lower in women compared to men (Men: 93 ± 3 vs. Women: 85 ± 2 mmHg, P=0.021) and MSNA tended to be lower in women compared to men (Men: 25 ± 3 vs. Women: 20 ± 2 bursts/min, P=0.091). After adjusting for mean BP and HR (partial correlation), CFPWV was significantly correlated with MSNA in men (R=0.44, P=0.021) and women (R=0.58, P=0.004). Interestingly, further adjustment for age abolished the association between CFPWV and MSNA in men (R=0.01, P=0.968), but not in women (R=0.43, P=0.046). A moderate relation between carotid β-stiffness and MSNA was observed in men (R=0.37, P=0.063) and women (R=0.44, P=0.034), but was abolished after adjusting for age (Men: R=-0.001, P=0.995; Women: R=0.26, P=0.245). These preliminary data demonstrate that MSNA is positively correlated with central arterial stiffness in women and men independent of BP. Furthermore, abolishment of the relation between MSNA and CFPWV in men only when adjusting for age suggests that the association between MSNA and central arterial stiffness may be more robust in women.

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Sympathetic Responses to Valsalva's Manoeuvre Following Bed Rest

Canadian Journal of Applied Physiology ◽

10.1139/h03-025 ◽

2003 ◽

Vol 28 (3) ◽

pp. 342-355 ◽

Cited By ~ 11

Author(s):

J. Kevin Shoemaker ◽

Cynthia S. Hogeman ◽

Lawrence I. Sinoway

Keyword(s):

Blood Pressure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Bed Rest ◽

Pressure Control ◽

Burst Frequency ◽

Nerve Activity ◽

Head Up Tilt ◽

Valsalva's Manoeuvre

The purpose of this study was to examine whether 14 days of head-down tilt bed rest (HDBR) alters autonomic regulation during Valsalva's manoeuvre (VM) and if this would predict blood pressure control during a 60° head-up tilt (HUT) test. To examine autonomic control of blood pressure, we measured the changes in systolic (ΔSBP) and diastolic (ΔDBP) blood pressure between baseline and the early straining (Phase IIE) period of VM (20 sec straining to 40 mmHg; N = 7) in conjunction with changes in muscle sympathetic nerve activity (MSNA; microneurography) burst frequency (B/min) and total activity (%Δ) from baseline over the 20-sec straining period. MSNA data were successfully recorded from 6 of the 7 individuals. The averaged responses from three repeated VMs performed in the supine position were compared between the pre- and post-HDBR tests. Compared with the pre-HDBR test, a greater reduction in SBP, DBP, and MAP was observed during Phase IIE following HDBR, p < 0.05. The increase in MSNA burst frequency during straining was augmented in the post- compared with the pre-HDBR test, p < 0.0001, as was the Phase IV blood pressure overshoot, p < 0.05. Although all subjects completed the 20-min pre-HDBR tilt test without evidence of hypotension or orthostatic intolerance, the post-HDBR test was stopped early in 5 of the 7 subjects due to systolic hypotension. The responses during the VM suggest that acute autonomic adjustments to rapid blood pressure changes are preserved after bed rest. Furthermore, MSNA and blood pressure responses during VM did not predict blood pressure control during orthostasis following HDBR. Key words: muscle sympathetic nerve activity, blood pressure, orthostatic tolerance, head-up tilt

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Gender difference in age-related changes in muscle sympathetic nerve activity in healthy subjects

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.5.r1600 ◽

1998 ◽

Vol 275 (5) ◽

pp. R1600-R1604 ◽

Cited By ~ 45

Author(s):

Toshiyoshi Matsukawa ◽

Yoshiki Sugiyama ◽

Takemasa Watanabe ◽

Fumio Kobayashi ◽

Tadaaki Mano

Keyword(s):

Blood Pressure ◽

Young Women ◽

Sympathetic Nerve ◽

Healthy Subjects ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Nerve Activity ◽

Healthy Men ◽

Age Related ◽

Age Related Changes

Muscle sympathetic nerve activity (MSNA) was measured directly along with blood pressure at rest in 69 healthy women (20–79 yr old) and 76 age-matched healthy men (16–80 yr old). All were nonobese and normotensive. In the women and men the MSNA was positively correlated with age (women: y = 0.788 x − 5.418, r = 0.846, P < 0.0001; men: y = 0.452 x + 12.565, r = 0.751, P < 0.0001). The regression intercept of y was significantly lower ( P < 0.0001) in the women than in the men, and the regression slope was significantly steeper ( P < 0.0001) in the women. The MSNA was lower in women than in men among those <30 ( P = 0.0012), 30–39 ( P = 0.0126), and 40–49 yr old ( P = 0.0462) but was similar in women and men among those 50–59 ( P = 0.1911, NS) and ≥60 yr old ( P = 0.1739, NS). The results suggest that MSNA increases with age in women and men and that the activity is markedly lower in young women than in men but is markedly accelerated with age.

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Hyperoxia lowers sympathetic activity at rest but not during exercise in humans

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.5.r873 ◽

1991 ◽

Vol 260 (5) ◽

pp. R873-R878 ◽

Cited By ~ 27

Author(s):

D. R. Seals ◽

D. G. Johnson ◽

R. F. Fregosi

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Arterial Blood Pressure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Total Activity ◽

Burst Frequency ◽

Nerve Activity ◽

Arterial Blood ◽

Exercise In Humans

The primary aim of this study was to determine the influence of systemic hyperoxia on sympathetic nervous system behavior at rest and during submaximal exercise in humans. In seven healthy subjects (aged 19-31 yr) we measured postganglionic sympathetic nerve activity to skeletal muscle (MSNA) in the leg, antecubital venous norepinephrine concentrations, heart rate, and arterial blood pressure during normoxic rest (control) followed by 3- to 4-min periods of either hyperoxic (100% O2 breathing) rest, normoxic exercise (rhythmic handgrips at 50% of maximum force), or hyperoxic exercise. During exercise, isocapnia was maintained by adding CO2 to the inspirate as necessary. At rest, hyperoxia lowered MSNA burst frequency (12-42%) and total activity (6-42%) in all subjects; the average reductions were 25 and 23%, respectively (P less than 0.05 vs. control). Heart rate also decreased during hyperoxia (6 +/- 1 beats/min, P less than 0.05), but arterial blood pressure was not affected. During hyperoxic compared with normoxic exercise, there were no differences in the magnitudes of the increases in MSNA burst frequency or total activity, plasma norepinephrine concentrations, or mean arterial blood pressure. In contrast, the increase in heart rate during hyperoxic exercise (13 +/- 2 beats/min) was less than the increase during normoxic exercise (20 +/- 2 beats/min; P less than 0.05). We conclude that, in healthy humans, systemic hyperoxia 1) lowers efferent sympathetic nerve activity to skeletal muscle under resting conditions without altering venous norepinephrine concentrations and 2) has no obvious modulatory effect on the nonactive muscle sympathetic nerve adjustments to rhythmic exercise.

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Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90444.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. R891-R898 ◽

Cited By ~ 47

Author(s):

Friedhelm Sayk ◽

Alexander Vietheer ◽

Bernhard Schaaf ◽

Peter Wellhoener ◽

Gunther Weitz ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Blood Levels ◽

Burst Frequency ◽

Nerve Activity ◽

Healthy Humans ◽

Vascular Bed

Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-α and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean ± SE: 12.1 ± 2.9 vs. 27.5 ± 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 ± 3.1 vs. 60.6 ± 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.

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From Brain to Blood Vessel: Insights From Muscle Sympathetic Nerve Recordings

Hypertension ◽

10.1161/hypertensionaha.121.16490 ◽

2021 ◽

Vol 77 (5) ◽

pp. 1456-1468

Author(s):

John S. Floras

Keyword(s):

Blood Pressure ◽

Blood Vessel ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Sympathetic Outflow ◽

Nerve Activity ◽

Neurogenic Hypertension ◽

Age Related ◽

Nerve Recordings

Multiunit recordings of postganglionic sympathetic outflow to muscle yield otherwise imperceptible insights into sympathetic neural modulation of human vascular resistance and blood pressure. This Corcoran Lecture will illustrate the utility of microneurography to investigate neurogenic cardiovascular regulation; review data concerning muscle sympathetic nerve activity of women and men with normal and high blood pressure; explore 2 concepts, central upregulation of muscle sympathetic outflow and cortical autonomic neuroplasticity; present sleep apnea as an imperfect model of neurogenic hypertension; and expose the paradox of sympathetic excitation without hypertension. In awake healthy normotensive individuals, resting muscle sympathetic nerve activity increases with age, sleep fragmentation, and obstructive apnea. Its magnitude is not signaled by heart rate. Age-related changes are nonlinear and differ by sex. In men, sympathetic nerve activity increases with age but without relation to their blood pressure, whereas in women, both rise concordantly after age 40. Mean values for muscle sympathetic nerve activity burst incidence are consistently higher in cohorts with hypertension than in matched normotensives, yet women’s sympathetic nerve traffic can increase 3-fold between ages 30 and 70 without causing hypertension. Thus, increased sympathetic nerve activity may be necessary but is insufficient for primary hypertension. Moreover, its inhibition does not consistently decrease blood pressure. Despite a half-century of microneurographic research, large gaps remain in our understanding of the content of the sympathetic broadcast from brain to blood vessel and its specific individual consequences for circulatory regulation and cardiovascular, renal, and metabolic risk.

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