Women more susceptible to orthostatic hypotension

November 30, 2001

New study provides physiological basis that women are more susceptible to orthostatic hypotension than men

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.


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.


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.


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

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.

American Physiological Society

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