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New Study Provides Physiological Basis That Women Are
More Susceptible to Orthostatic Hypotension Than Men
Study results published in current edition of
American Journal of Physiology: Heart and Circulatory Physiology
November 27, 2001 -- Bethesda, Md. — The American Journal of
Physiology: Heart and Circulatory Physiology, one of the 14
peer-reviewed journals published by the American
Physiological Society (APS), spotlights recent research findings
designed to improve and understand human well and health. The November
edition includes a study focusing on the association of gender, erect
posture, and subnormal arterial blood pressure.
Introduction and Purpose
Individuals who experience symptoms such as lightheadedness and
palpitations while they stand are considered to have “orthostatic
intolerance.” According to the Vanderbilt University Autonomic Dysfunction
Center, “Many patients also note other symptoms with upright posture: visual
changes, discomfort in the head or neck, throbbing of the head, poor
concentration, tiredness, weakness, and occasionally fainting.” It is
estimated that up to 500,000 Americans have the disorder, which appears in
individuals less than 35 years of age, and affects women more frequently
than men.
Whereas most reports indicate that susceptibility for orthostatic
intolerance is more common in women than in men, the mechanisms of this
gender difference are unclear. The upright posture causes reductions in
venous return leading to diminished stroke volume (SV) and cardiac output (Qi).
To maintain blood pressure, the reduction in SV must be compensated for by
reflex mechanisms that increase total peripheral resistance (TPR).
Otherwise, blood pressure falls, leading to cerebral hypoperfusion and
syncope. Reports over several decades support the hypothesis that adequate
sympathetic constrictor responses during the assumption of upright posture
are critical for the maintenance of arterial pressure and cerebral
perfusion. Whether orthostatic sympathetic vascular control is different
between genders has not been investigated directly.
Gender differences in reflex-mediated sympathetic activation have only
recently attracted investigative attention. However, such studies have
focused on neural responses to nonbaroreflex stimuli. The results of these
earlier studies are equivocal in terms of whether or not gender differences
exist in sympathetic reactivity. Reports of lower plasma norepinephrine
concentrations in women during orthostatic stress suggest that sympathetic
outflow may also be diminished. However, plasma norepinephrine
concentrations are not a precise indicator of sympathetic outflow, and more
direct measures are required to determine gender differences in sympathetic
control during postural stress.
Thus the purpose of the current study was to test the hypothesis that
sympathetic adjustments to tilt are attenuated in women versus men, leading
to diminished blood pressure responses to head-up tilt (HUT). In addition,
measures of Qi and blood pressure were gathered to examine
systemic neurovascular control.
The results of the study, “Gender Affects Sympathetic and Hemodynamic
Response to Postural Stress,” conducted by J. Kevin Shoemaker and Derek S.
Kimmerly, at the Neurovascular Research Laboratory, School of Kinesiology,
University of Western Ontario, London, Ontario, Canada; Mazhar Khan and
Cynthia S. Hogeman, at the Division of Cardiology, Pennsylvania State
University College of Medicine, The Milton S. Hershey Medical Center,
Hershey, PA; and Lawrence I. Sinoway, at the Lebanon Veterans Affairs
Medical Center, Lebanon, PA, provide a physiological basis for the common
finding that women are more susceptible to orthostatic hypotension than
men.
The Study
A total of 17 healthy, nonsmoking, and normally active individuals
volunteered for the study, consisting of nine males (30 ± 11 yr, 176 ± 4 cm,
and 80 ± 12 kg; means ± SD) and eight females (26 ± 6 yr, 161 ± 8 cm, and
64 ± 12 kg). Two experimental procedures were performed on the subjects no
earlier than three hours after a meal and 12 hours after caffeine ingestion.
After establishment of baseline measures, data were collected during a
five minute period of supine rest, followed by a progressive HUT procedure
that included five minutes at each of 20, 40, and 60° of tilt. The subjects
were then returned to the supine position. After ~10 min of quiet rest, a
second baseline period was obtained, followed by insertion of a hand into
ice water (~4°C) for two minutes. During HUT, the increase in sympathetic
outflow is due primarily to baroreceptor unloading, whereas the cold pressor
test (CPT) elicits a nonspecific response. With the use of these two tests,
the researchers examined whether gender differences in sympathetic reflex
responses to HUT were present, and whether these were reflex specific.
Measurements
Heart rate was determined by standard electrocardiogram methods. Arterial
pressure was measured continuously from the finger of the left hand. The
hand from which blood pressure was obtained was maintained at heart level
throughout the testing periods, and baseline blood pressures were corrected
against manually obtained systolic and diastolic measures before the onset
of the data collection. Sympathetic activation was assessed by
microneurographic measures of muscle sympathetic nerve activity (MSNA) in
the common peroneal nerve. Cardiac SV velocity and aortic dimensions were
obtained to calculate Qi. Aortic diameter was obtained using
two-dimensional B-Mode echo Doppler imagine (2.5-MHz probe) with a
parasternal long-axis view of the aorta.
Data Analysis
Analog signals for blood pressure, MSNA, and SV velocity, sampled at
200 Hz, and for the electrocardiogram, sampled at 400 Hz, were collected.
Mean arterial pressure (MAP) was calculated as systolic blood pressure plus
one-third diastolic blood pressure. Pulse pressure (PP) was determined as
the difference between systolic and diastolic blood pressures. SV was
calculated as the product of SV velocity and the aortic cross-sectional area
for the mean cardiac interval. To diminish concerns that gender differences
in body mass and blood volume might interfere with interpretation of gender
differences in the hemodynamic responses SV was normalized to body surface
area (SVi) for all subjects.
Results:
Head-Up Tilt
Hemodynamics Baseline levels of heart rate, MAP, PP, SVi,
Qi, and TPR were not different in men and women. Heart rate and
MAP increased in both groups during HUT. Significant group- tilt
interactions were observed for heart rate and MAP (P < 0.002) and PP
(P < 0.004). Specifically, heart rate increased more in the females
than in the males (P < 0.05), and MAP increased more in the males
than in the females at 60° HUT. PP at 60° HUT was greater in the males
(67 ± 4 mmHg) than in the females (52 ± 4 mmHg) (P < 0.006).
A gender-tilt interaction was also present for the effect of tilt on PP
(i.e., P < 0.002). Specifically, at 60° HUT the PP was 12 ± 3.8
and 2.06 ± 3.34 mmHg for women and men, respectively (P <
0.001). SV and Qi decreased similarly in both groups
during HUT. At the highest tilt angle, SVi decreased
36 ± 7 ml/m2 in the males and 47 ± 4 ml/m2 in the
females (P = 0.11). The reduction in Qi at 60° HUT was
1.6 ± 0.5 l/min in the males and 2.0 ± 0.2 l/min in the females
(P = 0.31). TPR increased similarly in both groups.
MSNA Baseline MSNA burst frequency was 6.8 ± 1.6 beats/min
in females and 16 ± 2 beats/min in males (P < 0.07). Baseline burst
frequency normalized to heart rate (burst incidence) was higher in the males
(26 ± 4 beats/100 heartbeats) than the females (11 ± 2 beats/100 heartbeats;
P < 0.05). The baseline differences led to a main effect of group (P < 0.03)
with males demonstrating a consistently higher burst frequency during HUT.
Results:
Cold Pressor Test
Hemodynamics Heart rate and Qi were not altered
during the CPT in either male or female groups. MAP and TPR increased
similarly during the CPT in both males and females.
MSNA Compared with baseline, MSNA burst frequency and burst
incidence increased during the CPT (P < 0.05) in both men and women. Unlike
the HUT test, mean burst amplitude increased in both females (from 25 ± 4 to
33 ± 6 units; P < 0.02) and males (from 40 ± 4 to 58 ± 10 units; P < 0.002)
between baseline and CPT. However, when compared with the females, the total
MSNA response to the CPT was greater (P < 0.05) in the males due to a
similar frequency, but greater Mean burst amplitude (P < 0.05). Thus
the different response to a CPT in females versus males is qualitatively
similar to that for HUT.
Discussion and Conclusions
In the study, total MSNA during HUT was diminished in the females despite
lower MAP and smaller pulse pressures. The smaller sympathetic outflow
despite greater stimuli suggests that important differences exist in either
sensory afferent sensitivity or in the central integration and modification
of reflex input signals. Sensory signals contributing to the HUT sympathetic
response arise from cardiac chambers, aortic and carotid structures, and
from vestibular receptors. Otolithic vestibular afferents appear to
contribute to the orthostatic sympathetic response. However, available
evidence suggests that gender does not affect vestibulosympathetic
activation.
These data support the hypothesis that baroreflex sensitivity for control
of sympathetic outflow is diminished in women. The details regarding the
effect of gender on baroreflex sympathetic control remain unclear.
Furthermore, it is not known how regional vascular responses to sympathetic
excitation vary between males and females. As such, these data suggest that
blood pressure control during HUT differs in healthy men and women.
Source: American Journal of Physiology: Heart and Circulatory
Physiology, November 2001
-end-
The American Physiological Society (APS) was founded in
1887 to foster basic and applied science, much of it relating to human
health. The Bethesda, MD-based Society has more than 10,000 members and
publishes 3,800 articles in its 14 peer-reviewed journals every year.
***
Editor’s Note: For the full
text of the research cited above, or to set up an interview with a member of
the research team, please contact Donna Krupa at 703.527.7357 (direct dial),
703.967.2751 (cell) or djkrupa1@aol.com.
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