Download Mechanisms of Initial Blood Pressure Response to

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Clinical Science (1984)67, 321-327
Mechanisms of initial blood pressure response to
postural change
C . BORST, J . F . M .
VAN
BREDERODE, W . WIELING, G. A.
A N D A. J . DUNNING
VAN
MONTFRANS
Department of Medicine and Department of Cardiology, Academic Medical Centre, University of Amsterdam,
Amsterdam, and Department of Cardiology, University Hospital Utrecht, Utrecht, l%e Netherlands
(Received 26 Augustfl6 December 1983; accepted 15March 1984)
summary
1. The influence of supine rest on the blood
pressure response to standing and 70" head-up
tilt was studied in detail for the first 30 s after the
change of posture.
2. Following 20 min of supine rest, the active
transition to standing was accompanied by an
immediate increase in systolic pressure of 2 9 f 6
mmHg (mean SEM). This was followed by large
fluctuations in systolic pressure: to -28 2 mmHg
below control after 7 s and to 22 f 2 mmHg above
control after 22 s (17 mmHg in excess of the
systolic pressure level after head-up tilt).
3. Following 1 min of supine rest, there was
no difference in the immediate increase in systolic
pressure. However, the magnitude of the subsequent changes was significantly diminished.
4. With head-up tilt the immediate increase in
blood pressure was absent and afterwards small
changes were found that were also significantly
influenced by the period of prior rest.
5. Taken in conjunction with earlier studies,
the following mechanisms are suggested. The
immediate blood pressure increase resulted from
compression of arteries by the contracting postural
muscles. The subsequent blood pressure fall was
caused by at least two mechanisms; (a) the fall
was predominantly of reflex origin, because the
immediate pressure increase stimulated the
systemic baroreceptors; (b) supine rest possibly
augmented the translocation of blood from the
*
*
Correspondence: Dr C. Borst, University Hospital Utrecht, Department of Cardiology, Laboratory for Experimental Cardiology and Clinical
Physiology, P.O. Box 16250, 3500 CG Utrecht,
The Netherlands.
thorax which contributed, approx. 5 s from
standing, to the reflex fall of blood pressure.
Key words: arterial pressure, baroreceptor reflexes, catecholamines, head-up tilt, heart rate,
posture, rest, standing, supine.
Introduction
When normal subjects stand there are large fluctuations in heart rate and blood pressure lasting for
20-30 s [l]. There is an immediate increase in
heart rate which is mediated by withdrawal of
vagal tone [2, 31. This is attributed to a reflex
originating in the contracting postural muscles
and/or a 'central command' mechanism [4, 51.
There follows a further increase and a rapid decrease in heart rate accompanied by opposite
changes in arterial pressure, suggesting that the
heart rate changes are mediated by the arterial
baroreceptor reflexes [ 11.
In the present study a detailed comparison is
made of the changes in arterial pressure upon
standing and head-up tilt in relation to the period
of prior supine rest, and explanations are advanced
to account for the temporal response patterns.
Methods
Subjects
Eight subjects participated in the study after
giving informed consent. The investigative procedures were approved by the hospital ethical
committee. Three subjects were healthy male
volunteers, aged 25, 25 and 33 years. Five
subjects, four male and one female, mean age 37
years (28-53 years), were investigated as part of a
C. Borst et al.
322
larger study in which 24-h continuous intraarterial ambulatory blood pressure monitoring was
used to identify 'cuff-responders', i.e. subjects
without any evidence of target organ damage but
with a marked difference between casual readings
taken in the office and intra-arterial pressure at
rest at home. Untreated their office readings
were > 160 mmHg systolic/100 mmHg diastolic.
At home, intra-arterial blood pressure at rest was
121 2 6 mmHg (2SD) systolic and 73 6 mmHg
diastolic.
History,
physical
examination,
routine
laboratory tests and excretion urography or renography were all normal. They had no target organ
damage (fundi, chest X-ray, serum creatinine,
electrocardiogram and echocardiogram). Antihypertensive drug treatment was withdrawn, and
5 weeks afterwards 28-h continuous intra-arterial
ambulatory blood pressure registration was performed with the Oxford-Medilog system, which is
described fully elsewhere [6].
These subjects responded in a normal way to
static and dynamic exercise, mental stress tests
and the cold pressor test (G.A. Van Montfrans
e f al., unpublished work). The only abnormal
finding was an exaggerated rise in blood pressure
associated with taking a blood pressure reading
using the cuff method. As a result, for the purpose
of this study these subjects can be considered
normal persons.
_+
ing of muscles during the tilt. Although the
subjects were not strapped to the tilting table, the
tilting manoeuvre was considered a passive change
of posture.
Influence of supine rest
We compared the circulatory transients evoked
by standing after 1 and 20 min of supine rest. The
initial responses to 70" head-up tilt after 1 and
10 min of rest were compared in the same manner.
One minute supine rest was preceded by several
active changes of posture [ l ] . In this paper we
shall consider these conditions as 'no rest' and
'rest', respectively.
Plasma noradrenaline
Plasma noradrenaline was determined in four
subjects at the end of each brief or long supine
resting period according to the method of Endert
191, from venous samples obtained with an indwelling short brachial cannula that had been
introduced in the right arm before the experiment. Average plasma concentrations are given
for the rest and the no rest condition. In our
laboratory, the intra-assay and inter-assay coefficients of variation are 6% and 10% respectively. The detection limit is 32 ng/l [9].
Data analysis
Measurements
In seven subjects the blood pressure measurements were obtained with the Oxford-Medilog
system. The strain gauge was carried at heart level.
The data from one volunteer were taken from the
previous study [ 1] because supine control periods
matched the present protocol.
Instantaneous heart rate was derived from the
electrocardiogram and written on a pen recorder
as described before [ 1, 3, 71. The start of active
and passive changes of posture was marked on the
Oxford cassette tape and on the pen recorder with
the same push-button activated event marker.
The experiments were performed around 11.00
hours, following the 24-h blood pressure monitoring period at home. The subjects abstained from
coffee and smoking in the morning before the
measurements [8].
Comparison of standing and 70" head-up tilt
The changes of posture were accomplished as
described previously [ 1, 3 J in about 3 s. We used a
tilting table with foot support and anti-slip
mattress. Subjects were instructed to avoid strain-
Tape recordings were replayed at 25 times the
recording speed and the blood pressure signal was
displayed on an Elema-Schonander ink-jet
recorder running at a paper speed of 50mm/s,
with a sensitivity of 1 mm/5 mmHg (Fig. 1). We
measured systolic pressure (P,), diastolic pressure
(Pd) and heart rate (HR) in chronological order at
time t = -10, - 5 , 0, t(peak P,),3, t(minimum
Pd), t(minimum Ps), t(maximum HR), t(minimum HR), and 30 s (Fig. 2a, the minima and
maxima are indicated by arrows). Time zero was
defined as the start of the active or passive change
of posture. The choice of' sample points was
prompted by the results of the previous study [ 11.
The times the various minima and maxima
occurred were noted to 0.5 s. Both the magnitude and the timing of the various maxima and
minima were compared in the rest and the no rest
condition. When standing was compared with tilt,
the magnitude of the maxima and minima in the
response to standing were compared with the
values found at the same time after the onset of
head-up tilt.
Control values were averaged over 10 s before
the change of posture and the results were
Blood pressure response to standing
323
Results
501
-_-._
-- _-Supine Standing
5
0
10
20
15
Time (s)
Electrocardiogram
FIG. 1. Arterial pressure changes at the start of
standing. Skeletal muscle activity and baseline
changes were found in the electrocardiogram
during the stand up. Note the immediate, brief
increase in arterial pressure during the stand up.
Standing after 20 min of rest
On standing blood pressure increased abruptly
in all subjects. The increase of systolic pressure
reached a maximum of 29 f 6 mmHg (vs control,
P < 0.01) after 0.5-3 s (mean 1.4 s). After its
peak, arterial pressure quickly returned to control.
Between 2 and 4 s from standing it continued or
resumed its fall and after 6 k 1 s diastolic pressure
reached a minimum (-1 5 mmHg, P < 0.05 vs tilt).
The systolic pressure minimum (-28 mmHg) at
t = 7 f 1 s contrasted with the 8 mmHg decrease
observed at the same moment after tilt (P< 0.01).
expressed as changes from the supine control
values.
Statistical analysis
Results are presented as mean f SEM. The
Wilcoxon rank sum test was used to compare
groups. A P<O.O5 was considered to indicate a
significant difference.
I
I
-10
0
1
10
20
1
30-10
Systolic pressure ranged from 92 to 141 mmHg,
diastolic pressure ranged from 65 to 85 mmHg,
and HR ranged from 63 to 80 beats/min after 20
min of supine rest. Control values for standing and
tilt were not significantly different. The forced
respiratory sinus arrhythmia ranged from 11 to
36 (mean 23) beats/min, which indicates that vagal
HR control was normal [lo].
Fig. 1 shows an original record of the blood
pressure changes at the start of standing. Fig. 2
shows an example of the influence of supine rest
on the cardiovascular changes in a young volunteer.
The pronounced respiratory sinus arrhythmia
present at rest disappeared during the stand up.
The results in eight normotensive subjects are
summarized in Fig. 3.
-
0
10
Time (s)
u
20
30-10
0
10
20
FIG. 2. Examples of the heart rate and arterial pressure transients evoked by standing
up after 20 min of supine rest (a) and after 1 min of rest (b). The circulatory transients
induced by 70' head-up tilt after 1 min of rest (c) differed from the responses to the
active changes of posture. The arrows in ( a ) indicate the timing and the magnitude of
the minima and maxima of interest (see the Methods section). The heart rate changes
that are not related to the changes of posture were due to the respiratory sinus
arrhythmia. Plasma noradrenaline was 347 ng/l at the end of 20 min of supine rest
and 613 and 677 ng/l at the end of 1 min of rest before standing and tilt.
30
C. Borst et al.
3 24
Tilt
Standing
0,
0,
I
-10
-40 L
L
-10
ege!
0,1
1 min rest
20 min rest
0,
I
I
1
0
10
20
I
0
1
1
10
20
I
L
30 -10
min rest
10 min rest
I
0
I
1
J
10
20
30
L
I
1
1
1
30 -10
0
10
20
30
I
Op
v-:----I
a
2
2
-20
1
1
1
0
10
20
L
I
I
I
I
30 -10
0
10
20
30
J
Time (s)
Time (s)
FIG. 3 . Mean changes ( n = 8) f SEM in heart rate ( a ) , systolic ( b ) and diastolic arterial
pressure ( c ) induced by active (left panel) and passive changes of posture (right panel),
after a brief ( 0 ) and after a long period of supine rest ( 0 ) . The immediate pressure
increase upon standing is attributed mainly to mechanical compression of arterial
vessels by the muscular effort of standing. The immediate diastolic pressure increase
could not be determined reliably in some subjects and has been omitted.
When the HR increase reached its maximum of
33 f 3 beats/min (vs tilt, P < 0.01) at r = 11 1 s
diastolic pressure had recovered to the supine
control level but systolic pressure was still below
supine control (L6 mmHg). The HR increase
reached a minimum after 2 2 + 2 s ( - 6 beatdmin)
which undershot the response t o tilt (P<O.OS).
Systolic pressure showed an overshoot of 17
*
mmHg with respect to tilt (P< 0.01) after 22 s.
After 30 s there was little or no difference
between standing and tilt.
Comparison of 20 and I min of supine rest
Supine rest significantly modified the responses
to postural change (Figs. 2 and 3).
Blood pressure response to standing
325
Standing
Mechanism of immediate blood pressure increase
There was no significant influence of supine
rest on the immediate arterial pressure increase
after 1 s, on the primary HR increase at 3 s, or on
the minimum diastolic pressure. The fall of
systolic pressure, however, was 50% larger after
rest compared with no rest (P<O.Ol), and the
systolic and diastolic pressure minima were slightly
delayed. After rest the maximum HR increase
exceeded the increase without rest by 24% (P<
0.05) and was delayed by 2 s (P< 0.05).
The recovery of systolic pressure after 7 s was
accelerated after rest and was followed by a 17
mmHg overshoot with respect to tilt. No such
overshoot was found on standing without rest
(P< 0.05). Diastolic pressure recovery, however,
seemed to be independent of rest. After 0.5 min,
no significant influence of rest was observed on
the cardiovascular response to standing or tilt.
At the end of the long supine resting period,
plasma noradrenaline ranged from 204 to 514
ng/l. After arising several times, it was elevated
by 93 k 13% (P<O.Ol, Student’s t-test, n = 4)
when sampled at the end of the subsequent
1 min resting period. These values are within the
normal range in our laboratory [7 1.
The immediate increase in arterial pressure
upon standing (Figs. 1-3) may be attributed t o
several mechanisms: (1) a movement artefact,
(2) the immediate HR increase, (3) a reflex effect
of (static) exercise, (4) an increase in intrathoracic
pressure, (5) compression of arterial vessels, (6)
a cardiac output increase.
First, it is unlikely that it was a movement
artefact, because it was absent at the beginning of
head-up tilt and all measures designed to limit the
arm and cannula movements failed to reduce it.
Second, it cannot be caused by the HR increase
because handgrip evoked the same abrupt HR
increase without a concommitant blood pressure
increase [ 11. Third, the pressure increase cannot be
of reflex origin [4, 51, because the 29mmHg
peak was found after about 1 s, whereas reflex
vasoconstriction involves a 2-3 s delay and a
long time constant [ 11, 121, as illustrated by the
sluggish arterial pressure increase induced by
handgrip [l]. Fourth, we have no experimental
data on intrathoracic pressure, but when Valsalva
straining was intentionally avoided during contraction of abdominal and leg muscles, a similar
arterial pressure increase was observed [ 11. That
pressure increase has to be ascribed t o , fifth, the
mechanical increase of total peripheral resistance
caused by compression of arterial vessels in the
abdomen and the legs by contracting postural
muscles. We attribute the arterial pressure increase
during the stand up to the same cause. Sixth, it is
to be expected that contraction of postural
muscles compressed systemic capacitance vessels
as well [13]. It is possible that the immediate
blood pressure increase on standing was caused by
an increase in cardiac output [13, 141 due to an
increased right artrial pressure [13, 151. However,
we consider this mechanism less likely than the
previous one because of a too rapid increase and
decrease of the systemic pressure (Figs. 1 and 3 ) .
Loeppky et al. [14] reported a 1-2 s delay
between the start of exercise and an increase in
cardiac output measured by pulsed Doppler
echocardiography.
Discussion
Mechanism of blood pressure decrease
The principal finding was that supine rest did not
affect the initial blood pressure and HR changes
during the stand up, whereas it significantly
amplified the fluctuations in the next 30 s.
The present results confirm and extend a
preliminary report on blood pressure responses to
static muscle contractions and changes of posture
ill.
Two mechanisms probably contributed to the
blood pressure decrease that began after about 3 s.
(1) Passive translocation of blood from the thorax
resulted in the temporary predominance of a
cardiac output decrease over a reflex peripheral
resistance increase [16, 171, as illustrated by the
temporary fall of arterial pressure upon head-up
tilt (Fig. 3). (2) Stimulation of systemic baro-
Head-up tilt
Without prior rest, systolic and diastolic
pressure increased gradually upon head-up tilt.
After rest, however, a temporary small arterial
pressure decline (vs control, P < 0.05) was
observed, followed by recovery and rise of 5-10
mmHg above control.
Heart rate changes
In the initial 30 s of standing, HR and systolic
pressure changed mainly in the opposite direction.
Plasma noradrenaline
326
C. Borst et al.
receptors by the 29 mmHg pressure increase
during the stand up is expected to result in the
reflex decrease of arterial pressure after a delay of
2-3 s [ l l , 121. Whether brief stimulation of
cardiopulmonary receptors [13, 15, 18-20]
contributed as a third mechanism needs to be
examined.
Influence of supine rest
Fig. 3 suggests that the period of prior rest
affected the first but not the second component
of the arterial pressure decrease. Fig. 3 indicates
that, following rest, about one-third of the systolic
pressure decrease after standing was related t o the
change in posture itself, and two-thirds to the
reflex effect of the immediate pressure increase.
When the change of posture was not preceded
by rest, the first, passive component of the blood
pressure decrease seems to have been largely
absent, whereas the second, reflex component
was unaffected. The latter observation is consistent with the finding that rest did not modify
the immediate pressure increase.
The mechanism of the influence of rest on the
passive component of the blood pressure decrease
in unclear. It needs to be established whether the
translocation of blood from the thorax was
reduced in the no rest condition. If that can be
demonstrated, the elevated plasma noradrenaline
level found in that condition may have been
related to reduced capacity of the systemic capacitance vessels [21].
Mechanism of blood pressure recovery
The recovery of diastolic pressure after 6 s is
consistent with reflex vasoconstriction caused by
(1) decreased stimulation of systemic baroreceptors by the arterial pressure fall in the preceding
3 s (Fig. 3) [ 121, and (2) decreased stimulation of
cardiopulmonary receptors due to diminished
right ventricular filling pressure once t h e upright
posture has been attained [16-191. The mechanism of the influence of rest on the recovery of
systolic pressure remains to be determined.
Relation between heart and blood pressure
The present findings confirm and extend the
results reported previously [ l ] . The timing and
magnitude of the secondary [ 11 HR increase and
the subsequent minimum corresponded through
the arterial baroreceptor reflex largely to the time
course of the opposite systolic blood pressure
changes, because the latency of the vagally
mediated reflex HR changes [2, 31 is about 0.5 s
[12, 221. The simultaneous increase of HR and
blood pressure during the stand up was discussed
earlier [I].
Clinical implications
In testing for autonomic neuropathy [3, 10,
231, the HR response to standing has limited
diagnostic value in the individual patient because
the mechanism of the response is complex [ 1, 31.
Supine rest and an abrupt stand up increase the
the likelihood of dizziness approx. 5 s from standing. This dizziness will last only a few seconds. The
possible import of the present observations with
respect to recently reported accidents in the
elderly after arising suddenly [24] requires further
investigation.
Acknowledgments
We gratefully acknowledge the assistance of A. A.
Meijer, M. Pos and Dr S. A. Danner. We are
endebted to Professors J . J. Smith, J. T. Shepherd
and J. J. Faber for their valuable comments on the
manuscript. We thank W. van Eijsden for typing
the manuscript. This study was supported in part
by the Dutch Heart Foundation.
References
1. Borst, C., Wieling, W., van Brederode, J.F.M., Hond,
A., de Rijk, L.G. & Dunning, A.J. (1982) Mechanisms
of initial heart rate response to postural change.
American Journal of Physiology, 243 (Heart, Circulatory Physiology 12), H676-H681.
2. Ewing, D.J., Hume, L., Campbell, I.W., Murray, A,,
Neilson, J.M.M. & Clarke, B.F. (1980) Autonomic
mechanisms in the initial heart rate response to
standing. Journal of Applied Physiology, 49, 809814.
3. Wieling, W., Borst, C., van Brederode, J.F.M., van
Dongen Torman, M.A., van Montfrans, G.A. &
Dunning, A.J. (1983) Testing for autonomic neuropathy: heart rate changes after orthostatic manoeuvres
and static muscle contractions. Clinical Science, 64,
5 81-5 86.
4. Longhurst, J.C. & Mitchell, J.H. (1979) Reflex
control of the circulation by afferents of skeletal
muscle. International Review of Physiology, 18, 125148.
5 . Shepherd, J.T., Blomqvist, C.G., Lind, A.R., Mitchell,
J.H. & Saltin, B. (1981) Static (isometric) exercise.
Retrospection and introspection. Circulation Research, 4 8 (Suppl. l), 179-188.
6. Littler, W.A., Honour, A.J., Pugsley, D. J. & Sleight,
P. (1975) Continuous recording of direct arterial
pressure in unrestricted patients: its role in the
diagnosis and management of high blood pressure.
Circulation, 5 1, 110 1-1 106.
7. Wieling, W., Borst, C., van Dongen Torman, M.A.,
van der Hofstede, J.W.,van Brederode, J.F.M.,
Endert, E. & Dunning, A.J. (1983) Relationship
between impaired parasympathetic and sympathetic
Blood pressure response to standing
cardiovascular
control in
diabetes mellitus.
Diabetologia, 24,422-427.
8. Cryer, P.E., Silverberg, A.B., Santiago, J.V. & Shah,
S.D. (1978) Plasma catecholamines in diabetes: the
syndromes of hypoadrenergic and hyperadrenergic
postural hypotension. American Journal of Medicine,
64,407-416.
9. Endert, E. (1970) Determination of adrenaline and
noradrenaline in plasma by a radioenzymatic assay
using high pressure liquid chromatography for the
separation of the radiochemical products. Clinica
Chimica Acta, 96,233-239.
10. Wieling, W., van Brederode, J.F.M., De Rijk, L.G.,
Borst, C. & Dunning, A.J. (1982) Reflex control of
heart rate in normal subjects in relation to age. A
data base for cardiac vagal neuropathy. Diabetologia,
22, 163-166.
11. Borst, C., Karemaker, J.M. & Dunning, A.J. (1982)
Prolongation of atrioventricular conduction time by
electrical stimulation of the carotid sinus nerves in
man. Circulation, 65,432-434.
12. Borst, C. & Karemaker, J.M. (1983) Time delays in
the human baroreceptor reflex. Journal of the
Autonomic Nervous System, 9, 399-409.
13. Guyton, A.C., Douglas, B.H., Langston, J.B. &
Richardson, T.Q. (1962) Instantaneous increase in
mean circulatory pressure and cardiac output at
onset of muscular activity. Circulation Research, 11,
431-441.
14. Loeppky, J.A., Greene, E.R., Hoekenga, D.E.,
Caprihan, A. & Luft, U.C. (1981) Beat-by-beat
stroke volume assessment of pulsed Doppler in
upright and supine exercise. Journal of Applied
Physiology (Respiratory, Environmental and Exercise
Physiology), 50, 1173-1182.
15. Holmgren, A. (1956) Circulatory changes during
muscular work in man with special reference to
327
arterial and central venous pressure in the systemic
circulation. Journal of Clinical and Laboratory
Investigation, 24 (Suppl.), 1-97.
16. Gauer, H.D. & Thron, G.L. (1965) Postural changes in
the circulation. In: Handbook of Physiology: Section
2: Circulation, vol. 3, chapter 67, pp. 2409-2439.
American Physiological Society, Washington, DC.
17. Wolthuis, R.A., Bergman, S.A. & Nicogossian, A.E.
(1974) Physiological effects of locally applied reduced
pressure in man. Physiological Reviews, 54, 566595.
18. Donald, D.E. & Shepherd, J.T. (1978) Reflexes from
the heart and lungs: physiological curiosities or
important regulatory mechanisms? Cardiovascular
Research, 12,449-469.
19. Brown, A.M. (1979) Cardiac reflexes. In: Handbook
of Physiology: Section 2: The Cardiovascular System,
vol. 1 (The Heart), chapter 19, pp. 677-689.
American Physiological Society, Bethesda.
20. Ferguson, D.W., Thames, M.D. & Mark, A.L. (1983)
Effects of propranolol on reflex vascular responses
to orthostatic stress in humans. Role of ventricular
baroreceptors. Circulation, 67, 802-807.
21. Shepherd, J.T. & Vanhoutte, P.M. (1975) Veins and
Their Control, chapter 8 (Neural Control of Vascular
Capacity), pp. 134-152. W. B. Saunders Company,
London.
22. Pickering, T.G. & Davies, J. (1973) Estimation of the
conduction time of the baroreceptor-cardiac reflex in
man. Cardiovascular Research, 7, 213-21 9.
23. Mackay, J.D., Page, M.McB., Cambridge, J. &
Watkins, P. J. (1980) Diabetic autonomic neuropathy;
the diagnostic value of heart-rate monitoring. Diabetologia, 18,471-478.
24. LeCompte, P.M. (1983) Postprandial reduction in
blood pressure in the elderly (Letter to the Editor).
New England Journal of Medicine, 309,1255-1256.