Influence of sympathetic nerve activity on aortic hemodynamics and pulse wave velocity in women

Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.

Abstract

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure (P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women (P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women (P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women (P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group (P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.

NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.

central (aortic) blood pressure, aortic pulse wave characteristics, and arterial stiffness have been identified as measures of cardiovascular health and predictors of cardiovascular mortality (14, 18). Aortic pulse wave analysis (PWA) provides information on aortic blood pressure, which may be discordant with brachial blood pressure measurements, as well as the components of the aortic pressure waveform (14). Aortic blood pressure and other indexes of PWA, such as augmentation index (AIx) and augmented pressure, increase with age, as does cardiovascular risk (4, 24). Carotid-femoral pulse wave velocity (PWV), an index of aortic stiffness, also increases with age. Increases in central pulse pressure and arterial stiffness likely contribute to end-organ damage in the heart, kidneys, and brain (13). Furthermore, AIx is predictive of cardiovascular events in individuals with established cardiovascular disease (14), and PWV is considered to be an intermediate end point for fatal and nonfatal cardiovascular events after adjusting for traditional risk factors, such as obesity, hypertension, and smoking (14).

The sympathetic nervous system is a key regulator of blood pressure, and abnormal activity in this system is related to cardiovascular risk (5). Specifically, muscle sympathetic nerve activity (MSNA) increases with age and is positively associated with blood pressure in both older men and women (17). Moreover, in older postmenopausal women there is a positive correlation among MSNA and aortic blood pressure, AIx, and augmented pressure (10). In contrast, there is either no relationship or a negative relationship between these variables in young premenopausal women (3, 10). Little information currently exists on the association between MSNA and PWV in women. Observationally, the relationships between MSNA and the indexes of PWA have been described in women; however, it is not known if these relationships are causal or if the age-related increase in MSNA is responsible for higher aortic blood pressures, AIx, augmented pressure, and PWV in older postmenopausal women.

Therefore, the goal of this study was to determine if aortic hemodynamics and PWV are directly influenced by sympathetic nervous system activity in young premenopausal and older postmenopausal women. Our approach was to conduct measures of MSNA, PWA, and PWV at baseline and during ganglionic blockade with the drug trimethaphan camsylate. We hypothesized that the ganglionic blockade would significantly decrease aortic blood pressure, other indexes of PWA, and PWV in postmenopausal women but not in young women. We also hypothesized that the change in these variables would be related to baseline MSNA in postmenopausal women.

METHODS

Study Participants

A subset of this current data has been analyzed and published previously (1). Twelve young premenopausal women and 12 older nonsurgically induced, postmenopausal women provided written informed consent and completed the study. All women were self-described as white or Caucasian. Participants were normotensive, nondiabetic, nonobese (body mass index <30 kg/m²), nonsmokers, and free of cardiovascular and chronic diseases. Individuals were not taking medications with the exception of oral contraceptives in young women (n = 12) and medication used to treat hypothyroidism (n = 1) and osteoporosis (n = 1) in postmenopausal women. All young women were studied during the placebo phase of oral contraceptive use. Pregnant and breastfeeding women were excluded from the study; pregnancy status was confirmed by a urine pregnancy test within 48 h before the study day. Postmenopausal women taking hormone replacement therapy were excluded. Postmenopausal was defined as at least 12 mo since last menstrual cycle (8).

Experimental Protocol

This study was approved by the Mayo Clinic Institutional Review Board. All women underwent informed consent before study participation. Individuals refrained from alcohol, caffeine, and exercise for 24 h before the study; and following an overnight fast, participants were admitted to the Clinical Research Unit at the Mayo Clinic. Participants rested in the supine position during instrumentation and throughout the study. A 20-gauge, 5-cm catheter was inserted into the brachial artery of the nondominant arm using aseptic technique. A pressure transducer (model PX600F; Edwards Lifescience, Irvine, CA), positioned at heart level, was connected to the catheter to measure continuous beat-to-beat blood pressure. Heart rate was recorded continuously using a three-lead ECG (Cardiocap/5; Datex-Ohmeda, Louisville, CO). Data were collected at 250 Hz and stored via an offline computer using the WinDaq (DATAQ Instruments, Akron, OH) software system.

Measurements

Microneurography.

Multiunit MSNA was recorded at the peroneal nerve posterior to the fibular head using a tungsten microelectrode (1, 9). A reference electrode was placed subcutaneously ~3 cm from the recording site. The recorded signal was amplified 80,000-fold, band-pass filtered (700–2000 Hz), rectified, and integrated (resistance-capacitance integrator circuit, time constant of 0.1 s) by a nerve traffic analyzer. MSNA is expressed as burst frequency (bursts/minute) and burst incidence (bursts/100 heartbeats).

Pulse wave analysis.

Noninvasive assessment of arterial wave reflection characteristics was completed using the SphygmoCor system (AtCor Medical, Sydney, Australia) (3). High-fidelity radial artery pressure waveforms were recorded by applanation tonometry of the radial pulse in the right wrist using a pencil-type micromanometer (Millar Instruments). The radial blood pressure and waveform were calibrated from the systolic and diastolic brachial artery blood pressure (intra-arterial catheter). A generalized transfer function, which has been validated both intra-arterially (6) and noninvasively (7), was used to generate the aortic pressure waveform.

Pulse wave analysis of the aortic pressure waveform provided the following variables of interest: aortic blood pressures; pulse pressure amplification (the ratio between brachial pulse pressure and central pulse pressure); augmented pressure (AP; the difference between the first and second systolic shoulders of the aortic systolic blood pressure; i.e., the amplitude of the reflected wave); aortic augmentation index (AIx); AIx adjusted for a heart rate of 75 beats/min (AIx at 75 bpm); and wasted left ventricular pressure energy (Ew), which is the component of extra-myocardial oxygen requirement attributable to early systolic wave reflection (3). Ew can be estimated as [(π/4) × (AP × Δt_r) × 1.333], where 1.333 is the conversion factor for mmHg/s to dyn·cm²·s, and Δt_r is the systolic duration of the reflected wave. Only high-quality recordings, an in-device quality index of >80%, were accepted for analysis. Two-to-three measurements were performed to obtain two measurements within an acceptable quality index.

Pulse wave velocity.

Pulse wave velocity (PWV) was measured using the SphygmoCor system (AtCor Medical) (21). Carotid-femoral PWV (cfPWV or central PWV) was calculated by ascertaining the delay in the arrival of the arterial pressure waveform between the carotid and femoral sites in relation to the R wave of the electrocardiogram. Recordings were completed at the common carotid and femoral sites sequentially using applanation tonometry. Distance was defined as the distance between the common carotid and femoral recording sites, minus the distance of the common carotid recording site to the suprasternal notch. This distance (in meters) divided by the time delay of the pressure waveform (seconds) equaled cfPWV. The mean of two measurements is reported for each individual.

Systemic Ganglionic Blockade

Following initial instrumentation and baseline measurements, ganglionic blockade was completed using incremental intravenous infusion of trimethaphan camsylate (Cambridge Laboratories, Wallsend, UK). A complete ganglionic blockade was achieved when individuals demonstrated less than a five beats per minute increase in heart rate during phase II of the Valsalva maneuver (1, 25).

Statistical Analysis

All group data are reported as means ± SE. Demographic data, baseline variables, and MSNA levels of the two groups were compared using the Student’s t-test (SigmaPlot 12.0; Systat Software, San Jose, CA). Two-way repeated-measures ANOVA was utilized to determine if any significant group × condition interactions occurred for continuous variables (group: young vs. postmenopausal; condition: baseline vs. trimethaphan). Within-group comparisons between time points and between-group comparisons were completed using the Tukey’s post hoc test for multiple comparisons. An analysis of covariance (ANCOVA; IBM SPSS Statistics 22.00; IBM, Armonk, NY) was utilized to further examine the relationship between the decrease in peripheral blood pressure and the magnitude of change in cfPWV during trimethaphan infusion. Pearson correlation coefficients (r) were calculated to assess the relationships among MSNA, indexes of PWA, and cfPWV. A calculated P < 0.05 was considered significant.

RESULTS

Baseline Characteristics and MSNA Levels

Demographics and baseline MSNA levels for both young and postmenopausal (PM) women are shown in Table 1. These data were previously reported by Barnes et al. (1). PM women were significantly older than young women (P < 0.001). Body mass index and heart rate were similar between the groups (P > 0.05). PM women had higher baseline MSNA burst frequency and burst incidence than young women (P < 0.001 for both).

Table 1.

Demographic and baseline characteristics of study participants

Variable	Young (n = 12)	Postmenopausal (n = 12)
Age, yr	25 ± 1	61 ± 2*
Body mass index, kg/m2	24 ± 1	24 ± 1
Heart rate, beats/min	64 ± 3	58 ± 2
MSNA burst frequency, bursts/min	15 ± 1	33 ± 3*
MSNA burst incidence, bursts/100 heartbeats	25 ± 2	57 ± 5*

Data are presented as means ± SE. MSNA, muscle sympathetic nerve activity. Data previously published in Barnes et al. (1).

^*P < 0.001.

Brachial and Aortic Hemodynamics and Pulse Wave Characteristics

Brachial (arterial catheter) systolic and diastolic blood pressures, pulse pressures, and mean arterial pressures at baseline and during ganglionic blockade are reported in Table 2. These blood pressure variables decreased significantly in both young and PM women (P < 0.05 for all); however, systolic and diastolic blood pressures and mean arterial pressure decreased to a greater degree in PM women. Brachial pulse pressure decreased similarly in both groups. Further analyses of these data are detailed elsewhere (1).

Table 2.

Brachial and aortic hemodynamics at baseline and during trimethaphan ganglionic blockade

	Young (n = 12)		Postmenopausal (n = 12)
Variable	Baseline	Trimethaphan	Baseline	Trimethaphan	P Value for Interaction
Brachial SBP, mmHg	126 ± 4	110 ± 4*	141 ± 5†	94 ± 2*†	<0.001
Brachial, DBP, mmHg	73 ± 2	68 ± 3	71 ± 2	54 ± 2*†	<0.001
Brachial PP, mmHg	53 ± 3	42 ± 2*	70 ± 4†	40 ± 2*	<0.001
Mean arterial pressure, mmHg	91 ± 2	82 ± 3*	95 ± 2	67 ± 2*†	<0.001
Aortic SBP, mmHg	109 ± 4	96 ± 4*	134 ± 5†	86 ± 2*	<0.001
Aortic DBP, mmHg	75 ± 2	70 ± 3*	72 ± 2	55 ± 2*†	<0.001
Aortic PP, mmHg	34 ± 2	28 ± 2	62 ± 5†	31 ± 2*	<0.001
Pulse pressure amplification, %	157 ± 5	166 ± 5	117 ± 4	131 ± 4	0.28
Augmented pressure, mmHg	3.7 ± 1.7	1.4 ± 1.3	22.3 ± 2.9†	7.8 ± 1.2*†	<0.001
AIx, %	8.4 ± 4.1	3.4 ± 3.6	34.6 ± 2.8	23.5 ± 3.3	0.18
AIx at 75 beats/min, %	1.4 ± 4.3	7.8 ± 3.5	26.1 ± 2.3†	18.9 ± 2.9*†	0.005
Ejection duration, ms	337 ± 5	333 ± 6	355 ± 6	346 ± 7	0.54
Ew, dyn·cm2·s	768 ± 346	331 ± 268	5,157 ± 769†	1,702 ± 308*†	<0.001
cfPWV, m/s	6.5 ± 0.2	6.6 ± 0.2	8.8 ± 0.6†	7.5 ± 0.4*	0.003

Data are presented as means ± SE. SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; AIx, augmentation index; AIx at 75 bpm, augmentation index adjusted for a heart rate of 75 beats/min; Ew, wasted left ventricular pressure energy; cfPWV, carotid-femoral pulse wave velocity.

^*P < 0.05 vs. baseline within same group.

^†P < 0.05 vs. young at same time point.

At baseline, PM women had significantly greater aortic systolic blood pressure and aortic pulse pressure than young women (P < 0.05 for all; Table 2). During ganglionic blockade, aortic systolic and diastolic blood pressures significantly decreased in both young and PM women (P < 0.05); however, diastolic blood pressure decreased by a greater extent in PM women. Aortic pulse pressure was higher in PM women at baseline and decreased to levels similar to those in young women during trimethaphan infusion. Augmented pressure, AIx at 75 bpm, and Ew were also significantly greater in PM women vs. young women before trimethaphan infusion (P < 0.05). While these variables significantly decreased in PM women during ganglionic blockade, they remained higher than those in young women during this condition. There were no significant group × condition interactions for pulse pressure amplification, AIx, or ejection duration (P > 0.05).

Baseline MSNA burst incidence was positively associated with baseline aortic pulse pressure and Ew in PM women (r = 0.650, P = 0.02; r = 0.629, P = 0.03, respectively) but not in young women (r = −0.476, P = 0.12; r = −0.316, P = 0.32, respectively). Baseline MSNA burst incidence was not related to baseline augmented pressure or AIx at 75 bpm in either group (data not shown). We focus on MSNA burst incidence, as it takes into account heart rate and because heart rate increased significantly during ganglionic blockade (1). In PM women, baseline MSNA burst incidence was negatively related to the reductions in aortic pulse pressure (r = −0.633, P = 0.03), augmented pressure (r = −0.606, P = 0.04), and Ew (r = −0.669, P = 0.02) during ganglionic blockade (Fig. 1). In young women, baseline MSNA burst incidence was not related to decreases in aortic pulse pressure (r = −0.098, P = 0.76), augmented pressure (r = 0.044, P = 0.89), or Ew (r = −0.007, P = 0.98) during ganglionic blockade. Baseline MSNA burst incidence was not associated with the magnitude of change in AIx at 75 bpm in either PM (r = −0.216, P = 0.50) or young women (r = −0.116, P = 0.72).

Fig. 1.

Pearson correlation analysis of the relationships between baseline muscle sympathetic nerve activity (MSNA; burst incidence) and the changes in aortic pulse pressure (A), augmented pressure (B), augmentation index adjusted for a heart rate of 75 beats/min (AIx at 75 beats/min; C), and wasted left ventricular pressure energy (Ew; D) during trimethaphan ganglionic blockade in young and postmenopausal women.

Pulse Wave Velocity

Due to technical difficulties, we were unable to obtain a quality PWV recording in 1 young woman and 1 PM woman; therefore, 11 young and 11 PM women are included in the PWV data analysis. cfPWV at baseline was greater in PM women than in young women (P < 0.05; Table 2). With trimethaphan infusion, cfPWV did not change in young women but decreased significantly in PM women (P < 0.05). There were no longer differences in cfPWV between the groups during trimethaphan infusion.

Baseline MSNA burst incidence and baseline cfPWV were not related in either young or PM women (data not shown). Additionally, the change in cfPWV during trimethaphan infusion was not related to baseline MSNA burst incidence in either group (Fig. 2).

Fig. 2.

Pearson correlation analysis of the relationships between baseline muscle sympathetic nerve activity (MSNA; burst incidence) and the change in carotid-femoral pulse wave velocity (cfPWV) during trimethaphan ganglionic blockade in young and postmenopausal women.

An ANCOVA was completed to determine if ganglionic blockade would still result in a significant decrease in PWV in PM women after taking into account the reduction in blood pressure. The magnitude of change (Δ) in mean arterial pressure from baseline to that during ganglionic blockade was utilized as the covariate. The P value for the group × condition interaction for this analysis was P = 0.51.

DISCUSSION

In this study, there was an effect of age and/or menopausal status on aortic hemodynamics such that older postmenopausal women demonstrated greater baseline aortic systolic blood pressure, aortic pulse pressure, augmented pressure, AIx at 75 bpm, and Ew than young premenopausal women. Additionally, cfPWV was greater in PM women. Our new findings provide information on the contribution of sympathetic nerve activity on aortic hemodynamics and cfPWV in both young women and PM women. In agreement with our hypothesis, during ganglionic blockade, aortic systolic, diastolic, and pulse pressures decreased significantly in PM women, as did augmented pressure, AIx at 75 bpm, and Ew. In young women, only aortic systolic and diastolic blood pressures significantly decreased. Our correlation analyses indicate that baseline levels of MSNA are related to the decreases seen in aortic pulse pressure, augmented pressure, and Ew during trimethaphan infusion in PM women but not young women. These results suggest that aortic hemodynamics are highly dependent on sympathetic activity in older PM women in comparison to young women. Additionally, cfPWV was significantly reduced in PM women during ganglionic blockade but not in young women.

Previous data from our laboratory has shown that aortic systolic blood pressure, aortic pulse pressure, and pulse pressure amplification are positively associated with MSNA in postmenopausal women (10). Additionally, AIx, AIx at 75 bpm, augmented pressure, and Ew are positively related to MSNA in postmenopausal women (as well as young men) but are negatively related in young women (3, 10). In our current data set, statistically significant correlations or similar trends between MSNA and baseline aortic systolic blood pressure, aortic pulse pressure, augmented pressure, and Ew were seen in PM women. However, in young women, no statistically significant negative correlations existed between MSNA and baseline AIx at 75 bpm, augmented pressure, and Ew. We most likely did not see statistically significant negative correlations as previously shown because of our smaller sample size. Regardless, it appears that there may be both acute and chronic influences of MSNA on aortic hemodynamics in PM women. Acute blockade of catecholamine release from the sympathetic nervous system results in a decrease in arterial pressure and smooth muscle tone (2), significantly reducing aortic blood pressures, aortic pulse pressure, and aortic hemodynamic parameters in this group. Also in PM women, chronic structural changes in the aorta from sympathetically mediated endothelial dysfunction or fibrosis (18) may prevent some aortic hemodynamic variables, such as AIx at 75 bpm, augmented pressure, and Ew, from further decreasing to levels similar to those observed in young women. This may indicate the consequence of permanent vascular remodeling in aging, PM women.

No previous information exists regarding sympathetic activity in relation to PWV in women. We report for the first time that ganglionic blockade significantly reduces cfPWV in PM women but not in young women. However, this decrease in cfPWV is not related to MSNA; therefore, the changes in cfPWV seen during ganglionic blockade may be related to other hemodynamic variables. For example, because PWV is partially dependent on blood pressure, the dramatic decrease in blood pressure seen during ganglionic blockade may be a confounder in our results. The ANCOVA statistical analysis suggests that the reduction in mean arterial pressure as a result of the ganglionic blockade, rather than ganglionic blockade itself, is responsible for the decrease in cfPWV. Swierbleska et al. (20) reported a moderately strong, positive correlation between MSNA burst frequency and baseline cfPWV in healthy, normotensive men, before and after adjusting data for age and systolic blood pressure. In our data set, MSNA burst frequency and baseline cfPWV were not significantly associated in young women or PM women separately (data not shown). However, when grouping all women together, there is a significant positive correlation between the two variables before statistical adjustment (r = 0.469, P = 0.03). After adjustment for age and systolic blood pressure (similar to the analysis of Swierbleska et al.), the relationship between MSNA and cfPWV is no longer significant (r = 0.797, P = 0.52). This suggests that age and blood pressure may be more influential than MSNA in establishing baseline cfPWV in women than in men.

In a previous study by Barnes et al. (1), the analysis of heart rate was provided for the current cohort study of women and noted that heart rate increased to a greater degree in young women compared with PM women during ganglionic blockade (Δ21 ± 3 vs. Δ8 ± 3 bpm, P > 0.05, respectively). Because Wilkinson et al. (26) reported that an increase in heart rate, induced by incremental cardiac pacing, is associated with a decrease in augmentation index and ejection duration, the current study results should be interpreted in this context. In our study, a significant group × condition interaction was only noted for AIx after normalization for heart rate. Thus, suggesting differences in the magnitude of change in heart rate between groups during ganglionic blockade potentially masked the role sympathetic activity plays on AIx in aging women. Ejection duration did not significantly decrease in either young or PM women with ganglionic blockade, indicating a limited effect of the increase in heart rate on this parameter. It is important to note that in the study by Wilkinson et al. (26) incremental pacing led to an increase in peripheral blood pressures and central diastolic blood pressure while in this current report, ganglionic blockade resulted in significant decreases in peripheral and aortic blood pressures. Therefore, these two studies may not be directly comparable in all aspects.

In support of other data from our laboratory (1, 10, 11), this current report shows that regulatory factors (such as the autonomic nervous system and β-adrenergic receptors) within the cardiovascular system are altered with aging and menopause in women. It is unknown how much the decrease in female sex hormones that accompanies menopause contributes to our current findings, and previous studies are in conflict regarding the benefits of estrogen hormone replacement therapy on aortic hemodynamics and PWV. Miuria et al. (16) showed that postmenopausal women on hormone replacement therapy have lower brachial-ankle PWV in comparison to controls. Additionally, in a subset of nine women from that study, 4 wk of estrogen replacement therapy resulted in reduced PWV with no effects on blood pressure. Scuteri et al. (19) suggested that women on estrogen-only replacement therapy have a lower age-associated increase in systolic blood pressure, pulse pressure, and PWV than nonusers. In contrast, 1-2 yr of combined hormone replacement therapy did not result in aortic wave reflection or PWV changes in comparison to placebo (22, 23). The differences in these studies may be attributed to the types of hormone therapy used (estrogen only vs. estrogen-progesterone combination, as well as dose differences) and the duration of medication use. There are no studies observing the effects of hormone therapy on these parameters in conjunction with MSNA.

Limitations

In our cohort of women, all young premenopausal women were taking hormonal contraceptives at the time of the study. Therefore, this data may not be generalizable to women not taking these medications. However, previous studies suggest that hormonal contraceptives do not cause clinically significant alterations in AIx or PWV during the placebo or active pill phases in comparison to analogous phases of the menstrual cycle (12, 27). Thus repeating this study in premenopausal women who are not using hormonal contraceptives would not likely yield significantly different results.

Additionally, pharmacologically induced ganglionic blockade not only abolishes sympathetic and parasympathetic nerve activity but also reduces blood pressure and total peripheral resistance and increases heart rate. Therefore, the significant decreases in augmented pressure, Ew, and cfPWV in PM women may be confounded by the large reduction in blood pressure or elevation in heart rate, making this data somewhat difficult to interpret.

Due to our study design, the combined influence of age and menopause on the relationships among aortic hemodynamics, PWV, and MSNA were studied, and we are unable to tease out the individual effects of age vs. menopause on these variables. It is unclear if the dependency of aortic hemodynamics on sympathetic activity occurs as a woman ages or if it occurs during the menopausal transition or both. Casiglia and colleagues (4, 15) reported that while aortic systolic and diastolic blood pressures, AIx, and cfPWV are higher in older PM women vs. young premenopausal women, these differences can be accounted for by age alone (determined by statistically adjusted models). Additionally, this research group did not report any PWA or cfPWV differences between a subgroup of premenopausal women ages 50–59 yr and a subgroup of postmenopausal women ages 50–59 yr. However, characteristic details on these subpopulations (e.g., mean age, plasma sex hormone levels, time elapsed since menopause, etc.) were not reported, so further data interpretation is not possible.

Conclusions

We have demonstrated that multiple aortic hemodynamic parameters are negatively influenced by sympathetic nerve activity to a greater extent in older postmenopausal women than in young premenopausal women. Additionally, the effect of MSNA on cfPWV is primarily mediated through blood pressure in older postmenopausal women. A recent report from our laboratory suggests that blood pressure is more dependent on autonomic nervous system activity in older postmenopausal women than in young premenopausal women (1). Taken together, these findings support the idea that the increased sympathetic nerve activity that is seen with aging and menopause contributes to higher blood pressure and altered aortic hemodynamics in postmenopausal women, placing them at a higher risk of developing hypertension and other cardiovascular disease in comparison to their younger premenopausal counterparts.

GRANTS

Funding was provided by National Institutes of Health Grants RR-024150 (Center for Translational Science Activities; to R. E. Harvey), AG-038067 (to J. N. Barnes), AR-056950 (J. N. Barnes), HL-083947 (to M. J. Joyner), and HL-105467 (to D. P. Casey) and American Heart Association Grant 2170087 (to E. C. Hart).

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the author(s).

AUTHOR CONTRIBUTIONS

R.E.H. and J.N.B. analyzed data; R.E.H., J.N.B., and D.P.C. interpreted results of experiments; R.E.H. prepared figures; R.E.H. drafted manuscript; R.E.H., J.N.B., E.C.J.H., W.T.N., M.J.J., and D.P.C. edited and revised manuscript; R.E.H., J.N.B., E.C.J.H., W.T.N., M.J.J., and D.P.C. approved final version of manuscript; J.N.B., E.C.J.H., W.T.N., M.J.J., and D.P.C. performed experiments.