Orthostatic hypotension in aging humans

XIANGRONG SHI, D. WALTER WRAY, KEVIN J. FORMES, HONG-WEI WANG,

PATRICK M. HAYES, ALBERT H. O-YURVATI, MARTIN S. WEISS, AND I. PHILIP REESE
Departments of Integrative Physiology and Internal Medicine, University of North Texas Health
Science Center at Fort Worth, Fort Worth, Texas 76107
Received 11 November 1999; accepted in nal form 1 May 2000
Shi, Xiangrong, D. Walter Wray, Kevin J. Formes,
Hong-Wei Wang, Patrick M. Hayes, Albert H. O-Yur-
vati, Martin S. Weiss, and I. Philip Reese. Orthostatic
hypotension in aging humans. Am J Physiol Heart Circ
Physiol 279: H1548H1554, 2000.We tested the hypothesis
that hypotension occurred in older adults at the onset of
orthostatic challenge as a result of vagal dysfunction. Re-
sponses of heart rate (HR) and mean arterial pressure (MAP)
were compared between 10 healthy older and younger adults
during onset and sustained lower body negative pressure
(LBNP). A younger group was also assessed after blockade of
the parasympathetic nervous system with the use of atropine
or glycopyrrolate and after blockade of the
1
-adrenoceptor
by use of metoprolol. Baseline HR (older vs. younger: 59 4
vs. 54 1 beats/min) and MAP (83 2 vs. 89 3 mmHg)
were not signicantly different between the groups. During
40 Torr, signicant tachycardia occurred at the rst HR
response in the younger subjects without hypotension,
whereas signicant hypotension [change in MAP (MAP)
7 2 mmHg] was observed in the elderly without tachy-
cardia. After the parasympathetic blockade, tachycardiac
responses of younger subjects were diminished and associ-
ated with a signicant hypotension at the onset of LBNP.
However, MAP was not affected after the cardiac sympa-
thetic blockade. We concluded that the elderly experienced
orthostatic hypotension at the onset of orthostatic challenge
because of a diminished HR response. However, an aug-
mented vasoconstriction helped with the maintenance of
their blood pressure during sustained LBNP.
vagal dysfunction; tachycardiac response; lower body nega-
tive pressure; atropine; glycopyrrolate; metoprolol
ORTHOSTATIC HYPOTENSION, DEFINED AS a decrease in sys-
tolic blood pressure of 20 mmHg or in diastolic blood
pressure of 10 mmHg in upright posture, is prevalent
with aging (26). It has been reported that up to 30% of
normotensive subjects over 65 yr of age experience a
decrease in systolic blood pressure 20 mmHg during
60 head-up tilt (23). However, the incidence of ortho-
static hypotension observed in the elderly population is
frequently complicated by age-related pathological con-
ditions, such as high blood pressure (10, 14), or by
medications for these conditions, such as antihyperten-
sive agents (20, 30). Arterial blood pressure regulation
during orthostatic challenge, elicited by standing or
simulated by lower body negative pressure (LBNP),
appears to be functional in healthy, normotensive older
adults compared with their younger counterparts (29).
Although the arterial baroreex control of heart rate is
signicantly diminished with aging (17, 29), responses
of muscle sympathetic nerve activity (12) and venous
plasma norepinephrine concentrations (29) during hy-
potensive stimuli are not different between younger
and older adults. Because the neurally and humorally
mediated vasomotor responses take longer to be effec-
tive, it remains questionable whether elderly people
exhibit a greater hypotension at the onset of ortho-
static challenge compared with their younger counter-
parts. We postulated that aging contributes to the
attenuated response of arterial blood pressure regula-
tion at the onset of orthostatic challenge because of an
impaired tachycardiac response caused by an age-re-
lated vagal dysfunction. The purpose of this study was
to determine whether orthostatic hypotension was
present in older adults at the onset of LBNP-induced
central hypovolemia because of an age-related de-
crease in reex tachycardia. If the diminution of the
vagal function was the mechanism responsible for the
orthostatic hypotension in the older adults, then this
aging phenomenon would be imitated in younger sub-
jects after administration of a muscarinic cholinergic
(MC) antagonist to block the parasympathetic inu-
ence, thus simulating the age-related vagal dysfunc-
tion. Because the MC antagonist atropine penetrates
the blood-brain barrier and blocks both central and
peripheral MC receptors (21), we also chose the MC
antagonist glycopyrrolate, which presumably has little
central confounding effect (3) (24). Use of these two
drugs would allow differentiation of central modula-
tion of MC receptors on blood pressure regulation.
METHODS
Subjects
Ten (5 men and 5 women) younger subjects (25 1 yr old)
and 10 (5 men and 5 women) older subjects (64 1 yr old)
participated in the rst study. All younger and older subjects
were normotensive, without a medical history, and were
taking no medications during the study. Body weight (71.1
Address for reprint requests and other correspondence: X. Shi,
Dept. of Integrative Physiology, Univ. of North Texas Health Science
Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107 (E-mail:
xshi@hsc.unt.edu).
The costs of publication of this article were defrayed in part by the
payment of page charges. The article must therefore be hereby
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solely to indicate this fact.
Am J Physiol Heart Circ Physiol
279: H1548H1554, 2000.
0363-6135/00 $5.00 Copyright 2000 the American Physiological Society http://www.ajpheart.org H1548
4.9 and 74.0 5.0 kg, respectively) and height (173 3 and
171 3 cm, respectively) were similar between the younger
and older subjects. The second study tested 10 (7 men and 3
women) healthy younger adults (age, 24 1 yr old; weight,
71.0 4.1 kg; height, 177 4 cm) with and without the MC
antagonists atropine and glycopyrrolate. In addition, meto-
prolol was used to block 1-adrenoceptor in six younger
subjects. There was no gender-related difference in heart
rate (see Table 1). Arterial blood pressure tended to be lower
in young female subjects and higher in older female subjects
compared with their male counterparts, but the differences
were not statistically signicant (probably because of type II
or error). Heart rate and blood pressure responses to LBNP
were similar in both groups. After passing a physical exam-
ination, all subjects signed an informed consent form, which
explained the purpose and procedure of the experiments. The
experimental procedure and the consent form were approved
by the Institutional Review Board of the University of North
Texas Health Science Center at Fort Worth.
Procedure
Before the test, each subject was oriented to the laboratory
and familiarized with the experimental procedure and mea-
surements to be used during the test. Experiments were
carried out with the subjects lying supine, with the lower
body in a LBNP box.
Study 1. After the box was sealed, negative pressure was
preset at 15 Torr. The subjects body was prevented from
moving during LBNP by a cushioned saddle inside the box
between the subjects legs. After 30 min of supine rest,
baseline pulse interval (PI) or heart rate (HR) and systolic,
diastolic, and mean arterial blood pressures were continu-
ously recorded by an online personal computer. Immediately
after 1 min of baseline, negative pressure was established
and remained for 810 min. Cardiovascular variables were
continuously monitored during LBNP. After 10 min of
recovery from a LBNP of 15 Torr, the baseline data were
again collected, followed by the application of a preset LBNP
of 40 Torr for 810 min. All subjects were asked to breathe
15 times/min during data collection.
Study 2. The second group of younger subjects performed
two LBNP tests at 40 Torr on each experimental day.
Baseline HR and arterial blood pressure were continuously
collected for 1 min, followed by the application of LBNP for 15
min, which was preset at 40 Torr. After approximately 45
min of recovery from LBNP, atropine (n 8) was injected at
5 g/kg to fully block the MC receptors, i.e., there was no
further tachycardia observed after two consecutive doses, or
to a cumulative dose of 40 g/kg wt. The cardiovascular
responses to LBNP were then assessed. After 1 wk, subjects
returned to the lab to repeat the same protocol with glyco-
pyrrolate (n 8) as the MC antagonist. Glycopyrrolate was
injected at 2 g/kg until complete blockade was achieved or to
a cumulative dose of 16 g/kg. The dose of glycopyrrolate was
determined to be equipotent to that of atropine (2, 8, 22). The
test order was randomized. In addition, the responses of HR
and arterial blood pressure to a LBNP of 40 Torr were
tested in six young subjects before and after administration
of metoprolol, with a cumulative dose of 200 g/kg wt to
selectively block
1
-adrenoceptor.
Measurements
Experiments were conducted with ambient temperatures
between 24 and 26C and relative humidity between 55 and
65%. A standard lead II electrocardiogram was used to mon-
itor HR. For study 1, arterial pressure was continuously
measured by an intraradial arterial catheter (9 younger and
2 older subjects) or by a nger cuff (Finapres, Ohmeda) on the
middle nger. A sterile, disposable pressure transducer
(Cobe, Lakewood, CO) interfaced with the arterial catheter
was monitored by a dual-pressure channel monitor (Hewlett
Packard 78342A), and the reference point was set at the
subjects midaxillary line. During all experiments, the pres-
sure inside the LBNP box was continuously monitored.
Data Management
Data were reported in group means SE. Changes in PI
and systolic, diastolic, and mean arterial blood pressure
during the initial 10 pulses and during the whole 1st, 2nd,
3rd, and 8th min of LBNP were calculated as the cardiovas-
cular responses to the onset of and sustained orthostatic
stresses, respectively. Two-way analysis of variance
(ANOVA) was employed to determine the age and time (dur-
Table 1. Arterial blood pressure and PI before and during 40 Torr LBNP
Variable
Baseline Onset Response M1 M2 M3 M8
M W M W M W M W M W M W
MAP, mmHg
Younger 853 885 31 42 31* 21 21 12 31 21 11 32
Older 813 968 103* 155* 52* 73 41* 86 53 97 43 23
P value 0.718 0.390 0.710 0.729 0.784 0.350
SBP, mmHg
Younger 1265 1257 01 32 33 42 64 62* 73* 72* 72* 121*
Older 1186 13211 156* 217* 83 116 72* 149 84* 1510 84 55
P value 0.969 0.375 0.609 0.551 0.573 0.741
DBP, mmHg
Younger 682 695 31 22 11 22 11 32 01 32 21 32
Older 633 737 72* 104* 12 32 01 24 13 35 13 74
P value 0.860 0.563 0.658 0.863 0.862 0.120
PI, ms
Younger 1,114107 1,13850 20871* 12941* 15346* 16046* 22843* 18458* 22653* 23348* 22036* 27628*
Older 1,04968 1,08650 2415 8039 6020* 7723* 12030* 12013* 11028* 14816* 14129* 16336*
P value 0.415 0.811 0.736 0.649 0.572 0.239
Values are means SE; n 5 in either man (M) or woman (W) subgroup of both age groups. Arterial blood pressure and pulse interval
(PI) before and during lower body negative pressure (LBNP) of 40 Torr, with gender stratication. MAP, mean arterial pressure; SBP,
systolic arterial blood pressure; DBP, diastolic arterial blood pressure; onset response, mean response of the 1st to 10th pulses to the onset
of LBNP of 40 Torr; M1M8, data averaged from min 1 (including onset response), min 2, min 3, and min 8 during LBNP. *Signicant
change.
H1549 AGING AND ORTHOSTATIC HYPOTENSION
ing LBNP) factors (in study 1) or the effects of autonomic
nervous system antagonists and time in the younger group
(in study 2) on these cardiovascular responses. Duncans
method was used to compare the difference of the rst 10
pulse responses at the onset of LBNP. Tukeys methods were
applied for post hoc analysis during LBNP if ANOVA out-
come was signicant for the time (in min) factor. Statistic
Analysis System (SAS) software was utilized for the signi-
cance analysis. A P value 0.05 was considered to be signif-
icant.
RESULTS
Study 1
Because there was no signicant difference in either
baseline data or the responses of HR and arterial blood
pressure between men and women in both younger and
older groups (see Table 1), subjects had been merged
within the age groups. All subjects arterial blood pres-
sures were within the normotensive range. Mean and
diastolic arterial pressures tended to be higher in the
older subjects (see Table 2). However, none of these dif-
ferences reached a level of P0.05. HR or PI was statis-
tically identical in the younger and older subjects.
Arterial blood pressure during a LBNP of 15 Torr
was well maintained in both age groups (Fig. 1 and
Table 2). Baseline cardiovascular data before a LBNP
of 15 and 40 Torr were not statistically different in
either age group. When a LBNP of 40 Torr was
applied, a signicant systemic hypotension accompa-
nied by an absence of tachycardiac response within the
rst 10 pulses was observed in the older subjects (Fig.
2 and Table 3). In contrast, the younger group experi-
enced a signicant tachycardiac response at the onset
of LBNP without hypotension. However, the age-re-
lated difference in the change of arterial blood pressure
was absent after 1 min of LBNP of 40 Torr, despite a
signicantly diminished tachycardiac response in the
older subjects.
Study 2
Baseline PI, arterial blood pressure, and their re-
sponses to a LBNP of 40 Torr before atropine and
glycopyrrolate were not statistically different. There-
fore, these baseline data were merged into one control
group. MC antagonists increased HR (P 0.001) but
did not signicantly affect arterial blood pressure (Ta-
ble 3). The effect between drugs was not signicantly
different. During the control condition (i.e., before
drug), arterial blood pressure was well maintained,
Table 2. Blood pressure responses to LBNP
Variable B P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 M1 M2 M3 M8
15 Torr LBNP
MAP, mmHg
Younger 832 32 32 32 12 02 12 12 22 32 31 11 01 01 21
Older 893 32 22 32 32 32 42 52 52 42 42 22 22 22 43
P value 0.190 0.071 0.046 0.030 0.079 0.206 0.244 0.235 0.453 0.799 0.507 0.560 0.500 0.458 0.607
DBP, mmHg
Younger 651 32 32 32 21 11 02 12 22 21 21 01 11 11 01
Older 682 32 21 31 31 21 32 42 32 42 22 11 01 12 33
P value 0.361 0.032 0.021 0.014 0.060 0.189 0.231 0.252 0.482 0.402 0.638 0.551 0.483 0.451 0.387
40 Torr LBNP
MAP, mmHg
Younger 832 11 11 31 31 31 42 52* 62* 52* 41* 21 21 21 21
Older 925 72 103* 134* 134* 154* 164* 154* 144* 143* 123* 62 63 74 12
P value 0.190 0.002 0.006 0.010 0.017 0.007 0.010 0.026 0.036 0.029 0.038 0.057 0.157 0.229 0.656
DBP, mmHg
Younger 652 01 11 21 21 31 31 31 41 51 31 11 21 21 21
Older 714 72* 82* 102* 83* 93* 102* 102* 103* 92* 82* 21 12 23 33
P value 0.188 0.003 0.003 0.003 0.076 0.068 0.019 0.028 0.083 0.085 0.082 0.141 0.205 0.239 0.733
Values are means SE; n 8 in the younger group and n 9 in the older group during 15 Torr LBNP, and n 10 in both age groups
during 40 Torr LBNP. B, baseline data before LBNP; P1P10, responses of the 1st to the 10th pulses at the onset of LBNP. P value is
the outcome of ANOVA for the difference between the groups. *Signicant change from the baseline. Baseline data before 15 and 40 Torr
LBNP are not different in either younger or older group.
Fig. 1. Responses of pulse interval [change in () PI] and systolic
arterial blood pressure (SBP) within the rst 10 pulses at the onset
of lower body negative pressure (LBNP) and during min 1, min 2,
min 3, and min 8 of 15 Torr LBNP. Baseline PI and SBP before 15
Torr LBNP are similar between the younger (n 8; 1,048 77 ms
and 123 4 mmHg, respectively) and older (n 9; 1,118 37 ms
and 124 5 mmHg, respectively) subjects.
H1550 AGING AND ORTHOSTATIC HYPOTENSION
with a signicant tachycardiac response in the younger
adults (Fig. 3 and Table 3). However, after atropine or
glycopyrrolate to block vagal inuence, a systemic hy-
potension occurred, associated with a signicantly di-
minished tachycardiac response at the onset of LBNP.
This response was similar to that observed in the older
adults (Fig. 2). The changes in PI and arterial blood
pressure were similar between atropine and glycopyr-
rolate. During sustained LBNP, the difference among
the experimental conditions was insignicant.
Metoprolol tended to decrease HR (or PI) and to
enhance its response during a LBNP of 40 Torr (see
Table 4 and Fig. 4). However, none of these differences
reached P 0.05, according to the post hoc analysis.
Arterial blood pressure was similar before and after

1
-adrenoceptor blockade using metoprolol.
A systemic hypotension was inversely (P 0.05)
related to a tachycardiac response at the onset of a
LBNP of 40 Torr, indicating that a decrease in arte-
rial pressure was associated with a diminished tachy-
cardiac response. This correlation tended to be less
signicant in the older than in the younger subjects.
However, this correlation in the younger subject group
was disassociated after administration of either atro-
pine or glycopyrrolate.
DISCUSSION
The major nding of this study indicated that signif-
icant hypotension in normal, healthy older adults, but
not in the younger counterparts, occurred at the onset
of orthostatic challenge simulated by a LBNP of 40
Torr, suggesting that aging without complication of
diseases diminished the immediate response of arterial
blood pressure regulation. The underlying mechanism
appeared to be an age-related vagal dysfunction, be-
cause a similar systemic hypotension occurred in the
younger subjects after administration of the MC antag-
onist atropine or glycopyrrolate, whereas this response
was not affected by blocking the cardiac sympathetic
efferent inuence with metoprolol. However, the initial
orthostatic hypotension was not present during sus-
tained LBNP. Our data also suggested that a LBNP of
15 Torr did not signicantly decrease arterial blood
pressure in either the younger or older groups. Al-
though baseline HR in the supine position was rela-
tively lower in the older than in the younger subjects,
this difference did not reach a signicant level. A lower
baseline HR in the older adults may be related to a
decrease in the intrinsic HR with aging (16).
The present investigation demonstrated that the or-
thostatic hypotension observed in the older adults at
the onset of a LBNP of 40 Torr (Fig. 2) was related to
a diminished tachycardiac response. Clearly the onset
of orthostatic hypotension could not be attributed to a
decreased vasomotor response in the elderly, because
the reex response in muscle sympathetic nerve activ-
ity (12) or venous plasma norepinephrine concentra-
tion (29) during hypotensive stimuli appears unaffected
by age. Consequently, the increases in peripheral vascu-
lar resistance during steady-state LBNP, observed to
be similar between healthy older and younger subjects,
conrm our earlier ndings (27). Recent data implied
Fig. 2. Responses of pulse interval (PI) and systolic arterial pres-
sure (SBP) within the rst 10 pulses at the onset of LBNP and
during min 1, min 2, min 3, and min 8 of 40 Torr LBNP. Baseline
PI and SBP before 40 Torr LBNP are similar between the younger
(n 10; 1,081 58 ms and 122 4 mmHg, respectively) and older
(n 10; 1,112 35 ms and 129 6 mmHg, respectively) subjects.
Orthostatic hypotension is observed in the older subjects at the onset
of LBNP only. The SBP was not different between the groups from
min 2 LBNP, although tachycardia is still less in the older subjects.
*Signicant change from baseline. #Signicant change from baseline
plus min 1 data.
Table 3. Blood pressure responses of younger subjects during 40 Torr LBNP with
and without MC antagonists
Variable B P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 M1 M2 M3 M8
MAP, mmHg
C 862 22 22 32 22 12 02 12 02 12 02 01 11 21 31
A 883 82* 92* 103* 113* 103* 113* 123* 133* 133* 123* 52 32 42 42
G 945 101* 112* 122* 132* 143* 153* 163* 164* 155* 155* 54 24 13 45
P value 0.164 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.003 0.006 0.299 0.884 0.661 0.990
DBP, mmHg
C 671 11 22 21 11 12 12 02 12 02 12 01 01 01 21
A 712 83 103* 113* 113* 113* 114* 133* 143* 133* 133* 42 12 22 22
G 765 92* 102* 112* 132* 143* 153* 164* 164* 154* 145* 35 04 14 25
P value 0.111 0.002 0.001 0.001 0.001 0.001 0.001 0.002 0.002 0.005 0.006 0.484 0.899 0.727 0.992
Values are means SE. C, before drug (n 10); A, atropine (n 8); G, glycopyrrolate (n 8); MC, muscarinic cholinergic.
H1551 AGING AND ORTHOSTATIC HYPOTENSION
that a reex increase in forearm vascular resistance
was less in the older subjects in terms of unit increase
in muscle sympathetic nerve activity (11), probably
because of a desensitization of -adrenoceptor. How-
ever, the age-related difference in the vasomotor re-
sponse could not be responsible for the initial ortho-
static hypotension observed in the older subjects,
because the contribution of vasomotor tone to arterial
blood pressure regulation takes longer to be effective
(19). Our data indicate that the tachycardiac response
plays a crucial role in the maintenance of arterial blood
pressure at the onset of orthostatic challenge.
The reex tachycardiac response can be caused by
vagal withdrawal or sympathetic activation. The
present data conrm that vagal withdrawal was the
dominant factor for the rapid tachycardiac response in
the maintenance of hemodynamic homeostasis at the
onset of orthostatic stress, because the reex tachycar-
diac and arterial blood pressure responses to the onset
of LBNP at 40 Torr in younger subjects were not
different before and after selective blockade of cardiac
sympathetic inuence with the
1
-adrenoceptor antag-
onist metoprolol. However, after the administration of
MC antagonists in the younger adults, the tachycar-
diac responses were signicantly diminished, which
was associated with a signicant systemic hypoten-
sion. However, the difference in systemic hypotension
before and after MC receptor antagonists became sim-
ilar during sustained LBNP. The increases in HR (in
terms of beat/min) with MC receptor antagonists
tended to be greater after 1 min of LBNP, suggesting a
slower but an augmented cardiac sympathetic activity.
The difference in hemodynamic responses observed
between atropine and glycopyrrolate was insignicant,
although it has been noticed that a low dose of atropine
decelerates HR (21) as a result of the central mediated
antagonism (13). These data implied that the effect of
blocking central MC receptors with a high dose of
atropine was minor on the systemic hypotension that
occurred at the onset of the LBNP-simulated ortho-
static challenge. The altered response of the end organ
(i.e., heart) mediated by peripheral MC receptors was
the underlying mechanism for the initial orthostatic
hypotension.
Despite the presence of a systemic hypotension in
the older group at the onset of a LBNP of 40 Torr and
a persistent attenuation in the tachycardiac response
in the older subjects during a sustained LBNP of 40
Torr, there was no age-related difference in the change
of arterial blood pressure after 1 min of LBNP. These
data suggest that a neurohormonally mediated vaso-
motor response predominates in the maintenance of
Fig. 3. Responses of pulse interval (PI) and systolic
arterial pressure (SBP) of younger subjects at the
onset of LBNP and during min 1, min 2, min 3, and min
8 of 40 Torr LBNP with and without muscarinic
cholinergic antagonists. PI is signicantly decreased
(from 1,028 51 ms) to 604 22 and 567 19 ms after
atropine and glycopyrrolate blockade, respectively.
However, baseline SBP was not signicantly affected
by drugs (control, 123 3 mmHg, n 10; atropine,
126 3 mmHg, n 8; and glycopyrrolate, 128 5
mmHg, n 8). A signicant systemic hypotension is
observed in the younger subjects after vagal blockade
with the use of either atropine or glycopyrrolate, asso-
ciated with a substantially blunted tachycardiac re-
sponse at the onset of LBNP. During sustained LBNP,
the difference among 3 conditions is insignicant. *Sig-
nicant change from baseline.
Table 4. Blood pressure responses of younger subjects during 40 Torr LBNP with and without metoprolol
Variable B P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 M1 M2 M3 M8
MAP,
mmHg
C 864 12 02 12 02 02 11 11 11 11 22 01 21 32 22
M 865 22 32 22 02 32 31 41 41 21 11 21 11 22 32
DBP,
mmHg
C 693 12 12 12 12 01 01 11 11 21 11 01 01 02 01
M 684 22 22 22 02 31 31 11 31 21 21 01 01 01 21
Values are means SE; n 8 under both experimental conditions. C, before drug; M, after metoprolol treatment to block
1
-adrenoceptor.
H1552 AGING AND ORTHOSTATIC HYPOTENSION
arterial blood pressure during sustained orthostatic
challenge, and that this presence of an augmented
vasomotor mechanism in the healthy elderly compen-
sates for the age-related diminution of the tachycar-
diac response. Because the response of sympathetic
nerve activation was not signicantly different be-
tween the younger and the older adults (12, 29), this
augmented vasomotor response is likely mediated by
vasoactive hormones, such as angiotensin II, in the
older subjects. Without the vasoconstrictor compensa-
tion, however, the initial orthostatic hypotension
would lead to orthostatic intolerance or syncope, de-
spite the presence of a persistent tachycardiac re-
sponse during the orthostatic hypotension.
It has been known that a signicant central hypovo-
lemia can be developed by a LBNP of 15 Torr (15, 32),
yet there was no signicant hypotension in either the
younger or the older group of subjects in the present
study. It is generally accepted that a central hypovole-
mia during LBNP 20 Torr unloads both cardiopul-
monary and arterial baroreceptors (1, 15, 32) and that
the eliciting of orthostatic stress by LBNP of 50 Torr
is similar to passive standing or head-up tilt at 70,
as assessed by the changes in HR and blood pressure
(9, 31). It has been reported that muscle sympathetic
nerve activity can be activated by disturbing the ves-
tibular apparatus during head-down neck exion (28).
Degenerative changes in the peripheral vestibular ap-
paratus (6) and vestibular nucleus (4) occur with aging,
and the vestibular function appears to diminish in the
elderly (5, 7). The performance of the older subject
might be overestimated by LBNP-simulated ortho-
static challenge compared with head-up tilt test, be-
cause the tilt challenges a collective response mediated
by both the baroreex and vestibulosympathetic reex.
However, the inuence of the vestibular interaction
with the age-related vagal dysfunction on the cardio-
vascular responses remains to be elucidated during the
onset and the sustained orthostatic challenges.
The major limitation of this study is the lack of
stroke volume data, which could be different between
the younger and older subjects, affecting the arterial
blood pressure response. Arterial blood pressure is
regulated by both vasomotor tone and cardiac output,
the latter of which is the product of HR and stroke
volume. The left ventricular contractility, preload, and
afterload modify stroke volume. The arterial blood
pressure before LBNP was not statistically different
between the older and younger subject groups, nor was
it statistically different before and after the blockade of
MC receptors in the younger subjects. Thus changes in
afterload could not be responsible for the different
responses of arterial blood pressure or stroke volume at
the onset of LBNP of 40 Torr. Although reex vaso-
constriction is able to compensate for the preload-
induced reduction in stroke volume, this response re-
quires time to become fully effective. The absence of
systemic hypotension in both the older and younger
subjects at the immediate onset of LBNP of 15 Torr
indicated that the reduced preload in the rst few
heartbeats probably did not substantially alter stroke
volume. Thus the response of stroke volume as it con-
tributes to the regulation of arterial blood pressure at
the onset of orthostatic challenge is likely similar be-
tween the two age groups. It is generally accepted that
the ventricles are sparsely innervated by the parasym-
pathetic nerve bers, and the left ventricular contrac-
tility is primarily mediated by
1
-adrenoceptor of the
sympathetic nerve system (25). Downregulation of
1
-
adrenoceptor and adenylate cyclase activity (18) has
been observed with aging. However, neither arterial
blood pressure nor tachycardiac response was affected
by the blockade of cardiac
1
-adrenoceptors with the
use of metoprolol in the younger subjects, whereas a
systemic hypotension associated with the diminished
tachycardiac response after vagal blockade occurred at
the onset of a LBNP of 40 Torr. These data suggested
that the age-related difference in the sympathetically
mediated contractility could not be a determinant in
the immediate response of arterial blood pressure dur-
ing orthostatic challenge. Therefore, our postulation
was that the contribution of stroke volume to the reg-
ulation of arterial blood pressure at the onset of LBNP
was not signicantly different between the older and
younger subject groups. Rather, the diminished tachy-
cardiac response was responsible for the orthostatic
hypotension observed both in the older subjects and in
the MC-blocked younger subjects.
In summary, the present investigation indicated
that the orthostatic hypotension was present in
healthy older adults at the onset of LBNP of 40 Torr.
This systemic hypotension may explain why elderly
people experience more syncopal symptoms during
postural transitions to upright position during the ac-
Fig. 4. Responses of pulse interval (PI) and systolic arterial pres-
sure (SBP) of younger subjects at the onset of LBNP and during
min 1, min 2, min 3, and min 8 of 40 Torr LBNP with and without

1
-adrenoceptor antagonist metoprolol. Baseline PI shows the ten-
dency to increase with metoprolol (P 0.11), from 1,030 56 to
1,213 87 ms, and SBP is similar between two conditions, i.e., 121
4 vs. 119 4 mmHg (n 8). *Signicant change from baseline.
H1553 AGING AND ORTHOSTATIC HYPOTENSION
tivities of daily life. The underlying mechanism ap-
peared to be an age-related diminution of tachycardiac
response, probably due to vagal dysfunction. However,
an augmented vasoconstrictor response compensated
for the diminished reex tachycardia and maintained
arterial blood pressure during a steady-state ortho-
static challenge, if human aging was not complicated
with disease. We concluded that an orthostatic hypo-
tension was present in older adults during orthostatic
challenge, but an augmented vasomotor response pre-
vented syncope in healthy elderly individuals.
We are indebted to Dr. Peter B. Raven for continued support. We
also sincerely thank all our subjects for cheerful cooperation during
the experiment.
This study was supported by National Institute on Aging Grant
AG-14219, National Heart, Lung, and Blood Institute Grant HL-
45547, and the University of North Texas Health Science Center
Faculty Research grants.
This work was submitted in partial fulllment of the require-
ments for the degree of Master of Science for D. W. Wray, as
submitted to the Graduate School of Biomedical Science, University
of North Texas Health Science Center at Fort Worth.
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