Exp Physiol 101.

2 (2016) pp 219–229 219

Symposium Report

Sympathetic regulation of blood pressure in normotension

and hypertension: when sex matters
L. J. B. Briant1 , N. Charkoudian2 and E. C. Hart1
1
Clinical Research and Imaging Centre, Cardionomics Group, University of Bristol, Bristol, UK
2
US Army Research Institute of Environmental Medicine, Natick, MA, USA

New Findings
r What is the topic of this review?
Hypertension is a major problem in Western society. Risk of hypertension increases with
age, especially in women, who have lower risk compared with men until menopause. This
review outlines the sex differences in the sympathetic control of blood pressure and how these
mechanisms change with age.
Experimental Physiology

r What advances does it highlight?

It has recently been recognized that men and women regulate blood pressure by different
physiological mechanisms. This is important for both the understanding and the clinical
management of individual patients with hypertension. This review summarizes recent
advances in understanding how the regulation of blood pressure in hypertension by the
sympathetic nervous system differs between men and women.

The sympathetic nervous system has a central role in the regulation of arterial blood pressure
(BP) and in the development of hypertension in humans. Recent evidence points to differences
between the sexes in the integrative mechanisms by which BP is controlled, suggesting that the
development of hypertension may follow distinct pathways in women compared with men. An
important aspect of sympathetic control of BP is its substantial interindividual variability. In
healthy young men, the variability in sympathetic nerve activity (SNA) is balanced by variability
in cardiac output and vascular adrenergic responses, such that BP remains similar, and normal,
across a severalfold range of resting SNA values. In young women, variability in resting SNA
is similar to that seen in men, but the ‘balancing’ mechanisms are strikingly different; women
exhibit greater β-adrenergic vasodilatation compared with men, which minimizes the pressor
effects of a given level of SNA. Ageing is associated with increased SNA and a loss of the balancing
factors seen in younger people, leading to an increased risk of hypertension in older people.
Loss of oestrogen with menopause in women appears to be linked mechanistically with the
decrease in β-adrenergic vasodilatation and the increased risk of hypertension in older women.
Other important factors contributing to hypertension via sympathetic mechanisms are obesity
and arterial stiffening, both of which increase with ageing. We conclude with a discussion of
important areas in which more work is needed to understand and manage appropriately the
sex-specific mechanisms in the development and maintenance of hypertension.

(Received 29 September 2015; accepted after revision 14 December 2015; first published online 18 December 2015)
Corresponding author E. C. Hart: CardioNomics Research Group, Medical Sciences Building, Bristol BS8 1TD, UK.
Email: emma.hart@bristol.ac.uk


C 2015 The Authors. Experimental Physiology 
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220 L. J. B. Briant and others
Introduction
We know that young women are protected against
development of hypertension until around the age of
menopause. The details regarding mechanisms that confer
this antihypertensive effect are incompletely understood.
Over the last decade, there has been an increased focus on
how the female sex and sex hormones impact resting blood
pressure (BP) control. This is important because we do not
yet understand whether the mechanisms that lead to the
development of hypertension in men and women are the
same; does one’s sex impact how hypertension develops?
In this review, we discuss evidence for differences
in BP control in men and women via the autonomic
nervous system. In particular, we focus on how this
information might be used to start understanding how
essential hypertension develops in younger and older
men and women. Is there a different role for the
sympathetic nervous system in the onset and maintenance
of hypertension in women versus men?
Sympathetic regulation of blood pressure
Although both the parasympathetic nervous system and
the sympathetic nervous system (SNS) have equally
important roles in blood pressure regulation, this review
focuses on the SNS. Evidence shows that the SNS is
important in both short- and long-term control of blood
pressure. In the 1850 s, Claude Bernard first discovered that
sympathetic nerves innervated peripheral blood vessels in
rabbits (Bernard, 1853). Later, in 1921, Heinrich E. Hering
identified baroreceptors in the carotid artery (see historical
review by de Castro, 2009). Early approaches to treatment
of severe hypertension focused on medical and surgical
manipulation of sympathetic neural mechanisms and
were successful in long-term lowering of arterial pressure
(Hinton, 1948; Smirk, 1951; Anon., 1970). One of these,
β-adrenergic blockade, remains a common and effective
treatment for high BP. However, the SNS has become best
known for its regulation of short-term transients in BP, via
the arterial baroreflex (Fadel & Raven, 2012). In the present
review, we focus on the role of the SNS in long-term control
of the resting level of BP and the importance of sex-specific
integrative mechanisms in this context.
Despite a clear role of the SNS in the pathophysiology
of hypertension (Guyenet, 2006; Esler, 2010; Esler et al.
2010; Grassi et al. 2015), the importance of the SNS in the
long-term control of BP has been a matter of debate for
many years (Lohmeier, 2001; Esler, 2010; Esler et al. 2010;
Navar, 2010a,b). Evidence for the importance of the SNS in
long-term control comes from the earlier clinical studies
noted above and from more recent experimental studies
in which pharmacological ganglionic blockade decreased
BP in normotensive and hypertensive subjects in a manner
proportional to the initial level of sympathetic tone (Jones
Exp Physiol 101.2 (2016) pp 219–229
et al. 2001; Diedrich et al. 2003; Christou et al. 2005).
Other evidence shows that chronic carotid baroreceptor
stimulation evokes long-term reductions in sympathetic
nerve activity (SNA) and BP in conscious dogs (Lohmeier
et al. 2004) and human hypertensive subjects (Lohmeier
& Iliescu, 2011).
Recently, increased attention has been paid to what we
can learn from the chronic interindividual variability in
SNA about the role of the SNS in long-term BP control
(Hinojosa-Laborde et al. 1999; Dart et al. 2002; Hart et al.
2012; Hart & Charkoudian, 2014; Joyner et al. 2015). The
fact that the well-established variation in muscle SNA
[MSNA; measured using peroneal microneurography; see
Vallbo et al. (2004), Macefield (2013) and Charkoudian
& Wallin (2014) for reviews] in healthy humans was not
correlated with resting levels of BP perplexed investigators
for some years. To some, this suggested that the SNS
was not important in determination of resting BP in
healthy humans. However, several lines of evidence now
indicate that this variability in resting MSNA provides
important insight into the sympathetic regulation of
BP and, in fact, supports the central role of the SNS
in both short- and long-term regulation of arterial
pressure. Additionally, results of experiments over the past
decade have provided new information about the differing
role of the SNS in long-term BP control in men and
women.
Sex differences in sympathetic control of blood
pressure
Young men. The conundrum that resting BP is not
related to MSNA in young men (Sundlöf & Wallin, 1978;
Charkoudian et al. 2005; Narkiewicz et al. 2005; Hart et al.
2011a) was investigated by Charkoudian et al. (2005),
who found that MSNA was positively correlated with total
peripheral resistance (TPR) in young men but negatively
correlated with cardiac output. This was subsequently
confirmed in additional studies (Charkoudian et al. 2005,
2006; Hogarth et al. 2007). Furthermore, the extent to
which peripheral resistance vessels constrict in response
to a given amount of noradrenaline was shown to be less
in people with higher SNA, providing a second ‘balancing’
factor, which prevents healthy people with high MSNA
from having higher arterial pressure (Charkoudian et al.
2006). It therefore appears that in young men, the net effect
of high MSNA on BP at rest is minimized by the balancing
of increased TPR with decreased cardiac output and
by variation in vascular adrenergic responsiveness. The
MSNA–TPR–cardiac output relationships have recently
been demonstrated in a large (n = 63 young men), pooled
cohort (Fig. 1). This balancing influence of cardiac output
has been attributed to alterations in stroke volume, rather
than heart rate, because young men with higher MSNA
exhibit smaller stroke volumes (Hart et al. 2009). Cardiac

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Exp Physiol 101.2 (2016) pp 219–229 Sex differences in sympathetic regulation of blood pressure 221

output in young men, therefore, acts to buffer the effect
of high MSNA (and consequently high TPR) on blood
pressure.
Young women. Blood pressure in young women showed
a similar lack of correlation with MSNA (Narkiewicz et al.
2005), suggesting that the relationships among MSNA,
TPR and cardiac output would be similar to those seen
young men. Surprisingly, this was not the case. Hart
et al. (2009) demonstrated that young women with high
levels of MSNA did not necessarily have a high TPR
(and/or low cardiac output). Pooled data from larger
samples (n = 37 young women; Fig. 1) also show no
relationship between MSNA and either TPR or cardiac
output in young women (Hart et al. 2012). Indeed, recent
data demonstrated that sympathetic ganglionic blockade
using intravenous infusion of trimethaphan camsylate
caused much smaller decreases in BP in young women
compared with men or with older women (Barnes et al.
2014). This indicates that some other mechanism(s) must
contribute to vasoconstrictor tone and BP in young
women.
In young men, administration of noradrenaline via
the brachial artery evokes robust increases in forearm
vascular resistance (increased vasoconstrictor tone) that
are reproducible and dose dependent (Kneale et al. 2000;
Hart et al. 2011a). In contrast, young women demonstrate
no substantial vasoconstrictor response to noradrenaline
administration; these data are supported by investigations
of α-adrenergic receptor sensitivity in young women
(Freedman et al. 1987; Kneale et al. 2000). These findings
suggest that a postjunctional mechanism is balancing
the vasoconstrictor effects of noradrenaline in young
women. Indeed, Kneale et al. (2000) discovered that
the difference between men and women in the forearm
vasoconstrictor response to noradrenaline was removed
by prior infusion with the non-selective β-adrenergic
receptor antagonist propranolol. This suggested that the
β-adrenergic vasodilatation may offset the vasoconstrictor
response to noradrenaline infusion in young women

Young men, n = 63 Young women, n = 37

r =0.53, P < 0.001 r = –0.02
30 30
28
TPR (mmHg/I/min)

26
TPR (mmHg/I/min)

24
22 20
20
18
16 10
14
12
10
8 0
0 20 40 60 80 0 20 40 60 80
MSNA (bursts/100 heart beats) MSNA (bursts/100 heart beats)

Young men, n = 63 Young women, n = 37

r = –0.41, P < 0.001 r = 0.10
12 12
Cardiac Output (I/min)
Cardiac Output (I/min)

10 10

8 8

6 6

4 4

2 2
0 20 40 60 80 0 20 40 60 80
MSNA (bursts/100 heart beats) MSNA (bursts/100 heart beats)

Figure 1. The relationship of muscle sympathetic nerve activity (MSNA) to total peripheral resistance
(TPR; top panels) and cardiac output (bottom panels) in young men (left panels) and young women
(right panels)
Muscle sympathetic nerve activity (expressed as bursts per 100 heart beats) is positively related to TPR
but inversely related to cardiac output in young men. Conversely, there are no relationships between
MSNA and TPR or cardiac output in young women. Reproduced with permission from Hart et al. (2012).


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222 L. J. B. Briant and others
(but not in young men). The fact that the vasodilator
effects of β-adrenergic receptors can offset the systemic
control of MSNA on TPR in young women was first
demonstrated by Hart et al. (2011a). In that study,
propranolol infusion in young women unveiled: (i)
a positive relationship between TPR and MSNA; and
(ii) the ability of brachial noradrenaline infusion to
evoke vasoconstriction in the forearm. Interestingly, the
relationship between MSNA and mean arterial pressure
also became positive, suggesting that, in the absence of
the vasodilator effects of β-receptors, cardiac output does
not balance the vasoconstrictor effects of high MSNA in
young women. It would appear, therefore, that increased
β-adrenergic receptor vascular sensitivity does not simply
uncouple MSNA from vasoconstriction, but is also an
important component for the integrative maintenance of
normotension in young women.
What mechanisms underlie the increased β-adrenergic
receptor vascular sensitivity in young women? Studies
in rats have revealed that circulating female sex
hormones may provide an explanation. Ferrer et al.
(1996) discovered that oestrogen replacement in
ovariectomized Sprague–Dawley rats restored the
vasodilatory β-adrenergic responses of mesenteric arteries
to isoprenaline infusion. This response was abolished
when propranolol was administered. The method by
which oestrogen may increase β-adrenergic sensitivity
is unclear, but has been attributed to nitric oxide
mechanisms (Hart et al. 2012). Oestrogen is known to
stimulate endothelial nitric oxide synthase in vascular
endothelial cells, increasing nitric oxide production in
vascular endothelial cells (Hisamoto & Bender, 2005;
Moriarty et al. 2006; Miller & Duckles, 2008). Moreover,
β-adrenergic receptors cause vasodilatation in part by a
nitric oxide mechanism (Cardillo et al. 1997; Ferro et al.
1999; Queen et al. 2006; Jordan et al. 2001; Eisenach
et al. 2002). It is therefore possible that circulating
oestrogen in young women potentiates the vasodilator
effect of β-adrenergic activation by a nitric oxide
mechanism.
Menopause and sympathetic control of blood
pressure
As people age, resting BP increases (Rothwell et al. 2005)
along with MSNA (Jones et al. 2001; Narkiewicz et al.
2005). In women, menopause adds an extra complication
to the ageing process; the rate of rise in BP during
the menopause transition period is much greater than
that in men over the same age range (Narkiewicz et al.
2005). Additionally, MSNA is increased in older women,
during and after menopause. Along these lines, ageing
women begin to develop a positive relationship between
MSNA and arterial pressure (Narkiewicz et al. 2005; Hart
et al. 2009, 2011a); thus, MSNA becomes important
Exp Physiol 101.2 (2016) pp 219–229
in determining the resting BP in older women. This is
reflected in studies where ganglionic blockade reveals that
the autonomic support of BP in older postmenopausal
women is greater than in younger women (Barnes et al.
2014).
It appears that changes in β-adrenergic receptors may
underlie this altered neural–haemodynamic coupling;
the previously described β-adrenergic mechanism that
minimizes noradrenergic vasoconstriction in young
women (Kneale et al. 2000; Hart et al. 2011a) disappears
in postmenopausal women (Hart et al. 2011a) or becomes
smaller. These data suggest that β-adrenergic receptor
sensitivity to noradrenaline is reduced in postmenopausal
women, although this was not assessed directly by
Hart et al. (2011a). Whether these changes result from
reductions in circulating female sex hormones or are
secondary to ageing in this population remains to
be investigated. Interestingly, postmenopausal women
receiving transdermal oestrogen hormone replacement
therapy exhibit a reduction in blood pressure and
MSNA (Vongpatanasin et al. 2001), suggesting that the
vasodilator effects of β-adrenergic receptors can still be
recruited in postmenopausal women.
Ageing in men: sympathetic control of blood pressure
We know that MSNA is increased in older men (Sundlöf
& Wallin, 1978; Narkiewicz et al. 2005; Hart et al. 2012).
In contrast to younger men, older men exhibit a positive
relationship between MSNA burst incidence and blood
pressure, suggesting a lack of balance between MSNA,
TPR and cardiac output. In particular, the negative
relationship between MSNA and cardiac output is lost
in older men (Hart et al. 2009). This would explain the
MSNA-mediated increase in BP in this age group, if the
relationship between TPR and MSNA remained positive;
however, this relationship is also lost in older men (Hart
et al. 2009). Therefore, it would appear that factors other
than MSNA become important for maintaining vascular
tone and driving increases in BP in older men. Indeed,
Dinenno et al. (2002) reported that ageing in men is
associated with a reduction in forearm postjunctional
α-adrenergic responsiveness to endogenous noradrenaline
release. Furthermore, the contribution of sympathetic
activity to α-adrenergic vasoconstriction was reduced
in older men. Autoregressive techniques in men have
revealed that sympathetic neurovascular transduction in
response to isometric hand grip is reduced in healthy
ageing (Tan et al. 2013), further indicating that the
transfer of MSNA into vasomotor tone may be blunted
in older men. However, these previous studies focused
on changes in MSNA and vascular α-adrenergic receptor
sensitivity in healthy ageing men. The direct role of
SNA in the regulation of resting BP in older men with
cardiovascular disease is unclear. Interestingly, Vianna

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Exp Physiol 101.2 (2016) pp 219–229 Sex differences in sympathetic regulation of blood pressure
et al. (2012) indicated that, using beat-by-beat changes in
BP following a burst of MSNA, older men exhibit a larger
fall in blood pressure when no MSNA burst occurs versus
that in age-matched women. This suggests that MSNA
is important in the support of resting BP in older men.
Currently, there are no studies that report changes in
BP after ganglionic blockade in older men versus older
women.
Other sympathetic mechanisms contributing
to hypertension
Other important, sex-dependent physiological changes
that occur with age may influence neural–haemodynamic
interactions. Additionally, the neural–haemodynamic
interactions outlined above may also influence BP via
other mechanisms.
Sex, SNA, body composition and physical activity.
Obesity is known to increase SNA, contributing to the
development of hypertension [see reviews by Schlaich
et al. (2004), Davy & Orr (2009), Lambert et al. (2010)
and Smith & Minson (2012)]. Elevations in SNA soon
after initiation of a high-fat diet have also been detected
in rat (Muntzel et al. 2012) and rabbit models of obesity
(Armitage et al. 2012). Furthermore, exercise training has
been shown to reduce hyperactivity of the SNS and BP
in hypertensive subjects (see review by Mueller, 2007).
However, recent studies have reported that the positive
relationships between MSNA and adiposity typically
found in men are not present in overweight and obese
women (Tank et al. 2008; Brooks et al. 2015). This
sex difference may be related to differences in vascular
responsiveness to (the increased) MSNA in obese men
versus women and/or may be due to differences in
inflammatory mediators associated with obesity in women
versus men (Brooks et al. 2015).
Sex and the arterial baroreflex control of SNA. Another
important component of BP control is the arterial
baroreflex regulation of SNA. The arterial baroreflex is
an important negative feedback loop in the control of
arterial blood pressure (Lohmeier et al. 2004; Guyenet,
2006; Lohmeier & Iliescu, 2011; Fadel & Raven, 2012).
Changes in arterial pressure are sensed as changes in
stretch at the walls of baroreceptive areas, including the
carotid sinus and aortic arch. These changes elicit reflex
changes in sympathetic and parasympathetic control of
the heart and peripheral vasculature. The reflex responses
then serve to minimize or reverse the initial change in BP
or ‘error signal’. The sympathetic arm of this reflex is one
method by which the SNS tightly regulates BP. Given the
above discussion, one wonders what implications there
are for BP regulation in women, given that the coupling

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223
between MSNA and the vasculature in young women is
relatively weak. Recent data suggest that women may rely
more on baroreflex control of heart rate than on control
of sympathetic vasomotor tone, compared with men (Kim
et al. 2011).
In men, ageing is associated with a decrease
in baroreflex sensitivity (responsiveness) in control
of MSNA burst incidence (Studinger et al. 2009).
Furthermore, this decrease manifests as diminished
baroreflex responsiveness to falling (versus rising) BP
(Hart et al. 2011b). In fact, recent data from our group have
demonstrated that baroreflex modulation of MSNA burst
area is not diminished in older men and may therefore
be countering the diminished baroreflex control of MSNA
burst incidence (Briant et al. 2015).
Recent data have demonstrated that resting diastolic
BP in women is above the operating point for
sympathetic baroreflex activation, which may explain the
low firing rates and baroreflex sensitivities compared with
age-matched men (Wehrwein et al. 2010). With ageing,
women appear to have lower sympathetic baroreflex
sensitivities than men (Okada et al. 2011), a change that
is associated with stiffening of baroreceptive areas. These
reports of dysfunctional baroreflex in women may explain
why clinically documented hypotensive disorders of BP
regulation are more common in women than in men (Ali
et al. 2000). In contrast to this sex-dependent observation
is the increase in BP that occurs in both sexes with
age.
Augmentation index and MSNA. Reflected BP waves
due to arterial stiffening from the periphery back to
the aorta can increase aortic BP; properties quantified
by the augmentation index, AI (Lee & Oh, 2010).
If a reflected wave arrives earlier (because of stiffer
vessels) during systole, this augments the systolic aortic
BP. The AI is a useful marker of cardiovascular risk
(Nurnberger et al. 2002), being a strong independent
risk marker for premature coronary artery disease (Weber
et al. 2004), hypertension (Glasser et al. 1997) and
all-cause cardiovascular mortality (Vlachopoulos et al.
2010a,b). Interestingly, the AI is positively related to
MSNA measured at rest in young men, but not in young
women (Casey et al. 2011). In young women at rest, a
positive relationship between MSNA and AI is observed
only during β-adrenergic blockade (Casey et al. 2012),
further demonstrating that β-adrenergic receptors offset
the effect of MSNA on the vasculature. Therefore, the
uncoupling of MSNA to AI in young women may be
another mechanism by which young women are protected
against the early development of cardiovascular disease.
With ageing and menopause in women, the relationship
between MSNA and AI at rest becomes positive (Hart
et al. 2013). Consequently, postmenopausal women
with high sympathetic activity may be more at risk
224 L. J. B. Briant and others
for developing cardiovascular diseases or experiencing
adverse cardiovascular events. Taken together, these data
suggest that the female sex hormones protect against the
effects of MSNA on the cardiovascular system in part by
preventing augmented aortic pressures when MSNA is
high.
Other factors. Sex hormones have also been shown to
modify other factors related to SNA and blood pressure.
These include central arterial stiffness (Smith et al. 2001),
renin–angiotensin system and SNA interactions (Xue et al.
2005) and central control of sympathetic output (Saleh &
Connell, 2003).
Sex differences in sympathetic regulation of blood
pressure in essential hypertension
Sympathetic overactivity is now established as a major
contributing factor to the pathophysiology of essential
hypertension (Anderson et al. 1989; Schlaich et al. 2004;
Flaa et al. 2006; Guyenet, 2006; Fisher & Paton, 2012).
Previous studies demonstrating that the sympathetic
control of BP at rest is different between the sexes
have focused on normotensive men and women. An
important area for future research will be to investigate
how interindividual variability in neural–haemodynamic
relationships are altered when men and women become
hypertensive. In the context of the aforementioned sex
differences in neural–haemodynamic regulation, what can
be said about the roles of sex and age in hypertension?
In men, BP begins to increase during the third decade
of life, and the incidence of hypertension increases to a
plateau of 60–70% in the seventh decade (see Joyner et al.
2015). The progression of high BP in women is much
slower; it increases in the fourth and fifth decade (i.e.
during menopause) and continues to rise with age. By
the seventh decade, the rates of hypertension in women
exceed those in age-matched men. However, what is not
clear is whether there are sex-specific differences in the
mechanisms that lead to the development of hypertension
in the first place. We know that the development of
hypertension in humans is multifactorial; there is a role
for the renin–angiotensin–aldosterone system (Manrique
et al. 2009), baroreflex (Guyenet, 2006), chemoreflex (Kara
et al. 2003) and cerebral blood flow (Muller et al. 2012) in
the elevated SNA preceding hypertension. As discussion
of all these factors is beyond the scope of this review, we
focus specifically on the role of MSNA in elevating BP in
hypertensive men and women.
Hypertension in young women: oral contraceptives.
Despite the multifactorial protection against hypertension
enjoyed by most young women, in some instances young
women do develop essential hypertension. We do not yet
Exp Physiol 101.2 (2016) pp 219–229
understand the role of the SNS in the pathogenesis of
hypertension in these women; we are unaware of any
evidence regarding sympathetic neural–haemodynamic
interactions in young hypertensive women. Often, young
women with hypertension are taking oral contraceptives,
which increase blood pressure slightly compared with
age-matched naturally menstruating women (Harvey et al.
2015), although the women often remain normotensive.
Oral contraceptive use has been shown to increase
the risk of developing hypertension by approximately
twofold after adjusting for family history of hypertension,
parity, physical activity, alcohol intake and ethnicity
(Chasan-Taber et al. 1996). Numerous studies have
demonstrated that MSNA was not increased in women
taking oral contraceptives at rest (Harvey et al. 2015)
and during various sympathoexcitatory challenges (Carter
& Lawrence, 2007; Carter et al. 2010), suggesting that
blood pressure may be increased owing to the influence
of oral contraceptives on sympathetic neurovascular
transduction, rather than an influence on sympathetic
nerve activity itself. Whether this is due to the interaction
between oral contraceptives and the protective effects of
β-adrenergic receptors is currently unknown. However,
these observations do highlight the need to include
information on sex, hormonal and reproductive factors
in research studies and the importance of sex-specific
physiology, treatment and health outcomes (Miller, 2014;
Miller et al. 2014).
Hypertension in older women. In postmenopausal
women with high MSNA, the diminished ability of
the β-adrenergic receptors to offset vasoconstrictor
tone may explain, in part, why the incidence of
hypertension increases in this population (Burt et al.
1995). Furthermore, acute increases in MSNA, e.g due
to mental stress, are likely contribute to the increased
risk of cerebrovascular and other cardiovascular-related
events in older women in the UK and USA (Rothwell
et al. 2005; Roger et al. 2012). Compared with the large
number of studies linking hypertension with SNA in
men, existing studies in postmenopausal women are few.
Hogarth et al. (2011) showed that MSNA is elevated
in postmenopausal hypertensive women when compared
with postmenopausal normotensive subjects. However,
MSNA in hypertensive postmenopausal women was lower
than that in age-matched hypertensive men, despite a
similar level of resting BP (Hogarth et al. 2008). The greater
increase in BP in response to a given change in SNA in the
postmenopausal hypertensive subjects might be explained
by increased transduction of MSNA into vasoconstrictor
tone that happens in postmenopausal women (partly
owing to loss of opposing β-adrenergic vasodilatation).
In this context, we previously suggested that the
transduction of MSNA into vasomotor tone may be greater
in hypertensive women compared with age-matched men

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Exp Physiol 101.2 (2016) pp 219–229 Sex differences in sympathetic regulation of blood pressure
(Hart & Charkoudian, 2014). Preliminary data from
our group suggest that this may be the case (Fig. 2);
transduction, as measured by the transduction ratio
[TPR/MSNA; see Jarvis et al. (2014) or Okada et al.
(2011)], was greater in hypertensive postmenopausal
women (n = 6) compared with age-matched hypertensive
men (P = 0.011; n = 6, one-way ANOVA, Bonferroni
post hoc test). Augmented sympathetic neurovascular
transduction may therefore be an important contributor
to the increased prevalence of hypertension in women
versus men in older age groups.
Large cross-sectional studies suggest that, along with
the higher incidence of hypertension in postmenopausal
women, women with hypertension tend to have poorer
control of their blood pressure, despite taking medication
(Oparil, 2006). This highlights the need to gain a
better understanding of the integrative mechanisms of
hypertension in women, thereby to inform hypertensive
treatment strategies specific to women. More studies
focusing on potential differences in the sympathetic
neural involvement in hypertension in men and women
1.0
**
Transduction ratio (TPR/MSNA)
0.8
0.6
0.4
0.2
0.0
en
en
en
om
om
TN
w
w
TN
TN
N
Figure 2. Sympathetic neurovascular transduction is reduced
in postmenopausal hypertensive women
Preliminary data (L.J.B Briant, A.E. Burchell, L.E.K. Ratcliffe,
A.K. Nightingale, J.F.R. Paton, E.C. Hart; unpublished data)
from our laboratory showing muscle sympathetic nerve
activity (MSNA; in bursts per minute) and beat-by-beat total
peripheral resistance (TPR) measured in postmenopausal
women with normal blood pressure (normotensive, NTN;
n = 11) and hypertension (HTN, n = 6) and in age-matched
NTN (n = 11) and HTN men (n = 6). The ratio of these two
values (TPR/MSNA) gives a measure of sympathetic
neurovascular transduction [see Jarvis et al. (2014) or Okada
et al. (2011)]. Transduction of sympathetic activity into vascular
tone was greater in HTN compared with NTN women
(P = 0.004) and in HTN men compared with NTN men
(P = 0.021). Interestingly, transduction in HTN women was
greater than that in HTN men (P = 0.011). One-way ANOVA,
Bonferroni post hoc test, ∗ P < 0.05, ∗∗ P < 0.01.

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are clearly needed to fill these important gaps in
understanding.
Summary and future directions
There is now a plethora of evidence pointing to stri-
king differences between men and women in the
sympathetic mechanisms that control resting BP. In
healthy, normotensive young women, transduction
of SNA into vasoconstriction is offset, in part, by
opposing β-adrenergic vasodilatation. This is likely to
be an important component of the decreased risk of
hypertension in younger women compared with men of
similar age. This protective effect of the β-receptors does
not extend to young men and is lost in postmenopausal
women, apparently linked to the loss of oestrogen at that
time. However, most of the existing research focuses on
healthy normotensive populations. Given the growing
body of evidence that there are differences between
men and women in the contribution of the sympathetic
nervous system to resting BP regulation, it is likely that the
mechanism by which SNA is involved in the development
of hypertension is different between men and women.
In future work, it will be important to delineate further
*
the mechanisms by which sympathetic neural activity
*
contributes to BP regulation in hypertensive women.
For example, what are the mechanisms of transduction
of sympathetic neural activity into vasoconstriction
in hypertensive premenopausal women? How does
increased SNA cause hypertension in postmenopausal
women, and are these mechanisms different from those
in age-matched men? Clearly, focused research is needed
regarding sex-specific mechanisms of hypertension that
can further improve and individualize its management.
en
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Exp Physiol 101.2 (2016) pp 219–229 Sex differences in sympathetic regulation of blood pressure 229

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