Cardiovasc. Res., 1969, 3, 476-485.

Cardiovascular and Respiratory Changes During Sleep

in Normal and Hypertensive Subjects
J. D. BRISTOW,*A. J. HONOUR,
T. G. PICKERING,~
and P. SLE[GHT
From the Cardiac and Regius Professor of Medicine’s Departments, Radcliffe Infirmary, Oxford

AUTHORS’ SYNOPSIS.Thefall of bloodpressure accompanying sleep in man is largely due to a dimin-

ished peripheral resistance. Subjects with normal and raised arterial pressure show qualitatively and
quantitatively similar haemodynamic changes during sleep, except that the baroreflex sensitivity in
hypertensives is decreased, both awake and asleep.

Sleep, once described as “the diastole of the
cerebral beat” (Duckworth, 1881) is now generally
thought to be an active process, with distinct
brain-stem mechanisms necessary to produce the
two types of sleep-orthodox or slow wave sleep,
and paradoxical or rapid eye movement (REM)
sleep (Jouvet, 1967). The autonomic nervous
Accepted March 4, 1969.
* Present address: University of Oregon Medical School,
Portland, Oregon, U.S.A.
t M.R.C. Fellow. Reprint requests to T.G.P., Cardiac
Department, Radcliffe Infirmary, Oxford.
system shows a redistribution of activity in sleep,
the general trend being towards an enhancement of
parasympathetic over sympathetic activity, with
miosis and bradycardia. Both blood pressure
and heart rate fall, and it has been recently shown
by Smyth, Sleight, and Pickering (1969) that in
man the heart rate-blood pressure reflex is actively
maintained during these changes. The present
study, from the same laboratory, was of a further
series of subjects and, in addition, cardiac output
and blood gas changes were measured, and normal
subjects compared with hypertensives.

Table 1. Subjects Investigated, Arranged According to their Mean Arterial Preswres Awake*

Subject Age Sex MAP awake Diagnosis

no. (mm Hg)
1 36 M
2 46 M
3 24 M
4 23 F
5 39 M 89
6 24 M 90
7 45 F 92 Normal-referred for ? hypertension
8 48 M 93 Normal-referred for ? hypertension
9 58 M 104 Essential hypertension
10 55 F 111 +
Hypertension renal disease
11 35 M 112 Essential hypertension
12 50 M 1I4 +
Essential hypertension bronchiectasis
13 41 M 116 Essential hypertension
I4 55 F 118 +
Hypertension renal disease
15 50 M 120 Essential hypertension
16 44 M 131 Essential hypertension
17 52 F 136 Essential hypertension
18 29 F 137 Essential hypertension
19 55 M 130 Postural hypotension + chronic
bronchitis

* The dividing line between normals and hypertensives was arbitrarily taken as 100 mm Hg.
416
 Cardiovascular Changes During Sleep
Methods
Nineteen subjects were investigated; their ages
ranged from 24 to 58 yr. Some were volunteers with
normal blood pressure, whereas others had been re-
ferred for further investigation of hypertension. As
shown in Table 1, they were separated into two groups,
eight having mean arterial pressures (MAP) of less than
100 mm Hg-the normal group-and 10 with MAP of
more than 100 mm Hg-the hypertensive group. One
subject (No. 19) had severe chronic bronchitis and
postural hypotension, and was not included in either
group. The average age for the normal group was 35,
S.D. 10.6 yr, and for the hypertensives 47, S.D. f 8.9.
All the subjects slept for three consecutive nights in
the laboratory. On the first night systemic arterial
pressure was recorded every 5 min by an automatically
inflated sphygmomanometer cuff, as described by
Richardson, Honour, Fenton, Stott, and Pickering
(1964); on the second night continuous electroence-
phalogram (EEG) recording was added. During the
third night continuous recordings of brachial intra-
arterial pressure were obtained through a fine (1 mm
internal diameter) polyethylene cannula 15 in. long
connected to a Consolidated Electrodynamics strain
gauge by a 4 ft. polyethylene tube. Arterial blood
could be withdrawn through this without disturbing
the patient. A second cannula 9 in. long was inserted
into an antecubital vein for intravenous injections. The
Respiration --.-.----
Fig. 1. EEG changes during sleep and wakefulness. From above downwards: top five tracings EEG
(International 10-20 notation), EMG, eye movements, ECG, respiration, and brachial intra-arterial pres-
sure. Subject awake, BP= 170/90, in Stage 111 sleep, BP= 150/70, and in R E M sleep, BP= 155/75.
477
frequency response characteristics of the recording
system were determined by applying a square wave
pressure pulse at the cannula tip: the time constant was
25 msec and the resonant frequency 11 c/s. Respiration
was recorded by a pneumograph round the chest con-
nected to another strain gauge, and the electrocardio-
gram (ECG) from two precordial electrodes. The
EEG was taken from five pairs of bipolar electrodes on
the right hemicranium; eye movements and submental
electromyogram (EMG) were recorded as described
previously (Smyth et al., 1969). The different stages of
sleep and wakefulness were defined according to the
criteria of Gastaut and Broughton (1965). Typical
records showing the 10 channels used are shown in
Fig. 1.
Baroreflex Sensitivity
Rapid intravenous injections of angiotensin (0.25-
1.0 pg) or phenylephrine (25-100 pg), flushed in with
10 ml. saline, were used to produce brief rises of arterial
pressure of up to 30 mm Hg, with consequent reflex
bradycardia. After such an injection, each peak of
systolic pressure is correlated with the duration of the
pulse interval following the next beat; a linear plot is
obtained with a correlation coefficient of the order of
0.7-0.9. The slope of the line so obtained is an index of
baroreflex sensitivity, and is expressed in msec/mm Hg
---that is, the absolute increase in pulse interval produced
478 Bristow, Honour, Pickering, and Sleight
by a 1 mm rise in systolic BP. This method has been hypotension. The waking pressure was taken as
fully described by Smyth et a / . (1969). The lines ob- the average of 5 min readings whenever the subject
tained by either angiotensin or phenylephrine were was awake-before sleep, during wakeful periods
consistently repeatable (Bristow, Pickering, and Sleight, in the middle of the night, a n d after sleep, t o mini-
1969), and the results with phenylephrine were not mize changes due t o circadian rhythms. Readings
significantly different from those with angiotensin,
except that the occasional tachycardia at the end of the less than 5 min after a phenylephrine injection were
pressure rise seen with angiotensin was not found with excluded. The degree of fall of pressure was
phenylephrine. The responses to the two drugs have roughly proportional t o the waking pressure, the
been considered to be identical. The earlier subjects fall of MAP being 9.7, S.D.+8.3% (8.3 mrn Hg)
were tested with both, but later phenylephrine alone for the normals, and 11.7, S.D.k5.2% (13.4
was used. These injections were done throughout the m m Hg) for the hypertensives. Systolic pressure
night, without the subjects’ awareness of when they were fell more than diastolic, so that the pulse pressure
being performed. Most subjects had about 15 injec- was 6.0, S.D.k 3.2 m m H g less during sleep in the
tions in all. Control injections of saline had no effect normals, and 9.6, S.D. & 6.6 m m H g in the hyper-
on heart rate or blood pressure.
tensives. The lowest pressures were generally seen
Cardiac Output either in stage I V or R E M sleep. Results for the
two phases of sleep were analysed separately.
The Stewart-Hamilton dye dilution method was used,
with injections of 5 mg of indocyanine green flushed into Heart rate fell during sleep in all but four sub-
the venous cannula by 10 ml. saline. Blood was with- jects (subject 19 again showing n o change) a n d
drawn from the arterial cannula through a cuvette there was n o significant difference between the two
densitometer (Cambridge Instrument Co.) by a with- groups, the changes being 6,4, S.D. k 6.4%, or
drawal pump at 23 ml./min, and the resulting curve
recorded on film. All determinations were done in
5.0 beats/min for the normals, and 7.0, S.D. 5.1%, +
or 4.7 beats/min for the hypertensives. Waking
duplicate; MAP (by electrical damping of the arterial heart rates were slightly higher in the hypertensive
record) and heart rate were measured at the same time.
Most subjects had three such pairs of injections during group, but there was n o correlation between the
the course of the night. waking heart rate and the degree of bradycardia
with sleep; nor was there a coiisistent relationship
Blood Gases between the degree of fall OF pressure and the
Heparinized syringes were used to take 7 ml. samples degree of bradycardia for each subject, apart from
of arterial blood which were analysed immediately on a the fact that both tended to fall, as shown in Fig. 2.
Radiometer apparatus for pCO,., pOz, and pH. The All subjects were in sinus rhythm, although one
calibration was checked with standard gases and buffer (No. 15) had frequent premature atrial contractions
for each measurement. Each subject had at least four
such determinations during the night.
The third night of the study provided all the results
reported here. The subjects arrived at the laboratory
at 9.30 p.m., and recordings were started about 1) hr
later. Waking recordings were taken with the subject
lying quietly in bed, at least 30 min after the insertion
of the arterial and venous lines. Cardiac outputs were
recorded before the injections of phenylephrine or
angiotensin, as the latter might produce transient
changes in output. The samples for blood gases were
taken last of all, just before turning out the lights at
about 11.30 p.m. These procedures were repeated
throughout the night. The subjects were awakened
at about 4-5 a.m. and waking records were taken for a
further 30 min. None of the subjects was sedated, and
none was receiving hypotensive therapy at the time of
testing.

Results
Blood Pressure and Heart Rate
Values for each were taken every 5 min. There
was a fall of blood pressure with sleep (systolic,
diastolic, and mean pressures) in all but two sub-
jects, one of whom was subject 19 with postural
Fig. 2. Changes in heart rate plotted against changes in
mean arterial pressure occurring with sleep. Each point
represents one subject. Although both fall in most subjects,
there is not a consistent relation between the two for any one
subject. 0 =normal. 0 =hypertensive. W = postural
hypotension.
 Cardiovascular Changes During Sleep
Pulse 1 nterval
1200 m sec
1100
lo00
900
800
700 '
140
I
150
I
160
I
170
180
S y s t o l i c P r e s s u r e m m Hg
Fig. 3. Baroreflex changes with sleep in one subject. Each line represents one injection of phenylephrine.
A=average systolic pressure awake, both before and after sleep. S=average systolic pressure during
slow wave sleep.
which persisted throughout wakefulness and sleep,
and made calculations of the reflex sensitivity im-
possible.
Baroflex Sensitivity
Comparisons between waking and sleeping re-
flex sensitivity were made in 15 subjects. Hyper-
tension is characterized by a reduced baroreflex
sensitivity when tested by this method (Bristow,
Honour, Pickering, Sleight, and Smyth, 1969); the
normal group had a mean waking sensitivity of
14.8, S.D.f9.2 mseclmm Hg, and the hyperten-
sives 3.0, S.D. kO.9 msec/mm Hg. Subject 19
with postural hypotension had the lowest sensitivity
of all--0.3 msec/mm Hg.
The changes occurring in sleep in one subject (No.
18) are shown in Fig. 3, each line representing the
response to one injection of phenylephrine. The
averaged heart rate-systolic pressure relationships
for the whole night separated for wakefulness (A)
and sleep (S) are superimposed, and it can be
seen that, although the baroreflex mechanism is
still active during sleep, an alteration of the reflex
must have occurred to allow the different heart
rate-systolic pressure relationships which were
observed during wakefulness and sleep.
This alteration could be brought about either by
changing the slope of the lines-that is, altering the
sensitivity of the reflex-or by shifting the lines to
479
Subject No. 18
I
I
190 200
1 1
210
1
220
the left-that is, resetting the reflex-or by a com-
bination of the two. This is shown diagram-
matically in Fig. 4, where it is assumed that the
linear relationship which we have observed during
a transient pressure change represents a portion of
a sigmoid curve, as originally described for the
carotid sinus response by Koch (1 93 I).
The subject whose reflex changes are demon-
strated in Fig. 3 showed both phenomena. Her
reflex sensitivity increased from 4.1 mseclmm Hg
to 8.0 (P<O.OOl), and the lines obtained during
sleep are clearly separated from those of wakeful-
ness, indicating that resetting has occurred. To
obtain a quantitative index of resetting we have used
the vertical distance between the lines at an arbi-
trary reference pressure, which is the averaged wak-
ing systolic pressure A, and the measurement is
expressed in milliseconds (Fig. 5 ) . This index,
however, will be influenced both by changes of
slope of the lines and by shift of position. We have
separated these by drawing a line from the origin
of the averaged line for sleep parallel to the line
for wakefulness. This line represents the change
due to resetting alone, and its shift from the waking
line is given by R. The effect of altered sensitivity
is given by S. Positive resetting is taken as a shift
of the lines towards an increase in pulse interval
(and an increased reflex activity), and negative
resetting as the reverse.
480 Bristow, Honour, Pickering, and Sleight
a) CHANGE OF SENSITIVITY b) R E S E T T I N G c) B O T H
'ulse
iternl

Systolic Pressure
Fig. 4. Theoretical baroreflex changes with sleep. Heavy lines indicate observed phenylephrine induced
changes. These have been superimposed on theoretical S-shaped curves describing the bchaviour of the
reflex arc over a wide range of pressure. Resetting has occurred when the control pressure-pulse interval
relationship is altered, change in reflex sensitivity occurs with change of slope. A =awake. S=sleep.
0 =average control systolic pressure before injection.

Table 2 shows the changes occurring with sleep in
each of the 15 subjects tested, separated into changes
due to altered reflex sensitivity and those due to
resetting. Comparing these results with those
reported earlier (Smyth et al., 1969), we now find
only one-third of subjects increasing the slope of
their lines during sleep, compared with nine out of
10 in the earlier series. Indeed, in the present
series a significant fall of reflex sensitivity was as
common as an increase. One explanation of this
difference may lie in the lesser number of in-jections
carried out in REM sleep during the present study
(the results shown in Table 2 are only for slow wave
sleep). In all five of the subjects of this series
tested in REM sleep (four normals and one hyper-
tensive) there was an increase in reflex sensitivity
when compared with waking slopes. In the earlier
study, injections during REM sleep were obtained in
seven of the 10 subjects, and in six of the seven these
injections provided the highest slopes of the night.

Table 2. Buroreflex Changes with Sleep, Analysed According to Changes in Sensiticity and Resetting
I
Average slopes (msec/mm Hg) Pulse interval (msec) at rel'erence pressure
(average waking systolic pressure)
Subject Awake Injects., Asleep Injects., Differ- P Awake Asleep Differ- P Change due to
no. no. no. ence ence - altered
resettine.
I sensitivity
1 12.3 8 16.9 4 + 4.6 NS 940 1300 +360 <O.OOI + 260 + 100
2 8.5 5 10.1 4 + 1.6
- 8.2
< 0.02
< 0.001
1000
1040
1100
1240
+I00
+200
<0.001
<0.001
++ 250
60 + 40
- 50
3 22.4 8 14.2 5
4 29.3 10 26.3 3 - 3.0 < 0.05 910 1380 +370 <0.001 + 540 - 70
5 10.4 10 8.2 5 - 2.2 < 0.01 980 970 - 10 <0.05 0 - 10
6 23.5 6 13,6 4 - 9.9 < 0.002 1070 1440 +370 <O.OOI + 630 - 260
7 3.6 10 2.7 7 - 0.9 < 0.001 790 950 +I60 <O.OOI + 180 - 20
8 4.4 9 5.9 11 + 1.5 < 0.001 970 1040 + 70 <0.001 + 30 + 40
9 1.8 7 I .8 4 0.0 NS 810 900 + 90 <0.001 + 90 0
10 2.4 6 0.4 4 - 2.0 NS 810 830 + 20 <0.002 + 20 0
11 3.3 5 5.2 7 + 1.9 < 0.002 800 960 + 160<0.002 + 120 +- 40
13 3.9 10 2.6 2 - 1.3 NS 680 800 +120 NS + 85 25
16 2.7 6 3.8 6 + 1.1 NS 1120 1280 +160 <0.001 ++ 100
70 ++ 180
90
18 4. I 3 8.0 6 + 3.9 <0.001 820 1100 +280 <0,001
19 0.3 3 0.0 3 -0.3 NS 1 910 880 - 30 NS - 30 0
 Cardiovascular Changes During Sleep
The resetting of the reflex mechanism is much
more constant. In 12 of the 15 subjects it occurred
in the direction of lowered heart rate and blood
pressure (positive resetting); in another subject
(No. 13) resetting was insignificant; in subject No.
19, who had the smallest change in heart rate and
blood pressure, together with the lowest reflex
sensitivity, it did not occur, and in one other subject
(No. 6) it went the other way. The blood pressure
of this subject did drop with sleep (7 m m fall of
MAP), but his heart rate was unchanged.
The resetting that accompanied sleep was usually
only partially reversed o n waking, so that the lines
obtained after sleep were intermediate in position
between sleep and pre-sleep wakefulness. This was
seen in all 11 subjects for which such data were
available, and was reflected by the generally lower
blood pressure during the 30 min after sleep than
in the 30 min preceding it. This may well be due
to the early hour (4-5 a.m.) at which such post-
sleep testing was done, as other workers have found
that pre- and post-sleep levels are the same (Khatri
a n d Freis, 1967a), a n d there is a circadian rhythm
of blood pressure in addition to the effect of sleep
(Richardson et a/., 1964).
The degree of resetting in the two groups of
patients was significantly different ( P c O a ) , the
averages being +244, S . D . k 2 2 3 msec for the
481
+
normals, a n d 80, S.D. k 34 msec for the hyper-
tensives. This difference is due to the steeper
slopes of the normal subjects, as shown in Fig. 5 ,
which compares the changes shown i:i two subjects,
one normal and one hypertensive, who showed
similar changes in blood pressure and heart rate.
Resetting of the lines during R E M sleep was less
marked than changes in sensitivity; in three sub-
jects the lines were reset more during R E M sleep
than slow wave sleep and in two subjects less.
Cardiac Output
Measurements were carried out in 17 subjects
(seven normals, nine hypertensives, and subject
No. 19), with a total of 5 5 pairs of observations.
For each pair the mean difference between the two
determinations was f 6.4%, S.D. f4.5%. Two of
these subjects did not sleep and in both of these the
outputs measured early and late in the night, about
4 hr apart, were within 5% of each other.
There was no significant difference between the
waking outputs of the two groups, the average for
the normals being 5.1 5 , S.D. f.1.48 I./min, and for
the hypertensives 5.28 S.D. f 1.73 I./min.
During sleep the normals showed no consistent
change in cardiac output (sleep values compared
with average pre- and post-sleep waking values);

ASLEEP
Pulse Interval /’ Subject No. 1

AWAKE

Subject No. 12
ASLEEP

- /
J - k-.... AWAKE

800 - %
%
-@
1 I I I I I I I I I J
80 100 120 140 160 180
Systolic Pressure mm Hg
Fig. 5. Waking and sleeping slopes in a normal (No. I ) and a hypertensive (No. 12) subject. Lines
represent averaged values of individual injections. The shifts of the lines have been divided into the contri-
bution due to resetting (R) and due to change in sensitivity (S). These values are taken arbitrarily at
the waking systolic pressure.
482 Bristow, Honour, Pickering, and Sleight
there was a variable fall of 6.2% S.D. k 13.6% in the
hypertensives, but this change was not statistically
significant. The values obtained before sleep were
generally slightly higher than those after sleep.
Satisfactory measurements in REM sleep were
obtained in only two subjects (both with normal
pressures) and in both of these the levels were
higher than the mean values for waking or slow
wave sleep.
Total peripheral resistance (TPR), calculated
from cardiac output and MAP at the time of
measuring the output, fell significantly (P< 0.02)
in all but one subject (No. 9). There was a tend-
ency for larger falls of TPR to occur in subjects
with higher mean waking pressures. This, how-
ever, was not statistically significant because of the
one subject whose TPR increased markedly during
sleep. If his results are omitted (and this output
was a single measurement, not a pair) the relation-
ship does become significant (r = 053, P = 0.05),
as shown in Fig. 6.
Both groups of subjects showed bradycardia
during sleep, and if the heart rates at the time of
measuring cardiac outputs are taken, the calculated
stroke volumes show an insignificant (0.05 <
P<O.l) increase of 11.2 ml. for the normals, with
no change for the hypertensives.
Blood Gases
Forty-four observations were made in 10 sub-
jects. Waking values were normal in all but two
Fall of 1 P R with Sleep
Arbitrary units
70 80 90 1W 110 120 130 140
M A P Awake mm HS
Fig. 6. Fall of TPR with sleep plotted against waking MAP.
subjects, one of whom had bronchiectasis, and the
other of whom showed an unexpectedly low PaOz.
Changes observed in sleep were consistent in all
subjects.
The PaCOz rose by 4.0 S.1). k 1.8 mm Hg, the
PaOz fell by 5.4 S.D.kS.1 mm Hg, and the pH
fell by 0.014 S.D. & 0.012. There was no obvious
correlation with the depth of sleep, or the time of
night, except that the pH tended to be lower in the
latter part of the night. The subject who showed
the largest fall of PaOz ( I 3 mrn Hg), although not
the largest rise of PaCO2, was the only one who
snored persistently throughout the night. These
changes in blood gases were associated with brady-
cardia and hypotension during sleep.
REM sleep measurements were obtained in four
subjects: the PaOz and PaCOZ were no different
from the values seen during slow wave sleep, but
in three of the four the pH was lower during REM
sleep than at any other time.
On waking, the blood gases returned to approach
the pre-sleep levels, and, although the pH and pCOz
changes were not always fully reversed, the differ-
ences between pre- and post-sleep levels were in-
significant.
Discussion
The most constant haemodynamic changes with
sleep which we have observed were the fall of blood
pressure and of TPR, both of which occurred in all
but one subject (No. 19 for blood pressure, No. 9
for TPR). In all subjects except No. 19 sleep was
accompanied by a fall of MAP of about lo%,
and a fall of heart rate of 72;. Of the 10 hyper-
tensive subjects, seven still had a MAP of more
than 100 mm Hg during sleep, only two falling
below this level (the remaining subject did not sleep).
These pressure changes are similar to those re-
ported previously for normal subjects (Snyder,
Hobson, Morrison, and Goldfrank, 1964; Khatri
and Freis, 1967a) and hypertensives (Richardson
2.23 et al., 1964). Shaw, Knapp. and Davies (1963)
found that patients in the malignant phase of
hypertension showed very little change; all our
hypertensives were in the benign phase.
Such a fall of arterial pressure could either be
due to a fall of cardiac output, or to a fall of TPR,
or to a combination of both. Our results indicate
that the lower pressure during sleep is primarily
due to a fall of TPR, with an insignificant fall of
I
cardiac output occurring in hypertensives. The
150 only other measurements of cardiac output in man
during sleep are those of Khatri and Freis (1967a,
b), who reported a drop of 10% in normal subjects.
 Cardiovascular Changes During Sleep
They concluded that the fall of blood pressure was
due to the fall of cardiac output, as the calculated
TPR remained unchanged. In hypertensives,
however, they did find a fall of TPR. The reasons
for these differences are not clear, although their
subjects were all young healthy volunteers whose
output averaged 7.64 I./min, whereas ours was a
much more varied sample with an average output
of 5.19 l./min, so on these grounds alone we might
be less likely to detect a significant change.
Animal experiments on this problem have been
mainly concerned with the blood pressure fall
during REM sleep in the cat; and the cat differs
from man in that the pressure falls to persistently
lower levels during REM sleep than at other times.
However, Zanchetti's group (Kumazawa, Baccelli,
Guazzi, Mancia, and Zanchetti, 1967; Guazzi,
Mancia, Kumazawa, Baccelli, and Zanchetti, 1968)
have found that the fall in blood pressure is largely
due to a fall of TPR, since denervating the heart
in sino-aortic deafferented cats made no difference
to the change in blood pressure with sleep, and
vagotomy (both surgical and pharmacological)
prevented the bradycardia but not the hypotension.
They concluded that . sleep hypotension is
' I . .
fundamentally dependent on peripheral vascular
phenomena."
The role of the baroreceptors in human sleep has
been discussed previously (Smyth et a/., 1969), al-
though in this series we have found changes due
to resetting more important than changes of reflex
sensitivity. Resetting of the baroreceptors is a
well-known concomitant of renal hypertension in
animals (McCubbin, Green, and Page, 1956)
and in man (Bristow, Honour, Pickering, Sleight,
and Smith, 1969), but in these cases it is thought to
occur at the receptor end of the reflex arc, whereas
the reversible resetting and altered sensitivity seen
in sleep are presumably centrally mediated.
Sino-aortic deafferentation in cats permits
catastrophic falls in blood pressure during sleep
(Guazzi and Zanchetti, 1965), even though these
Variable Normals
(n= 8)
_ _ ~ -
MAP -9.7% (S.D. 8.3%)
Heart rate -6.4% (S.D. 6.4%)
Cardiac output No change
TPR - 16.7% (S.D. 7.1%)
Stroke vol. Inconstant rise
Baroreflexes
a. sensitivity Variable change
h. resetting +244 msec (S.D. 233 msec)
483
animals were hypertensive when awake; the same
workers have subsequently shown that it is the
chemoreceptors rather than the baroreceptors which
normally prevent such changes (Guazzi, Baccelli,
and Zanchetti, 1968). The subject in our series
who most closely resembled the sino-aortic de-
afferented cats was the bronchitic with severe
postural hypotension (No. 19). In fact his blood
pressure and heart rate showed almost negligible
change with sleep (see Fig. 2), and his lesion is more
likely to be on the efferent side of the reflex arc.
The contribution which the baroreceptors make
to the regulation of cardiac output and TPR is a
controversial one, in animals no less than in man.
The evidence suggests that baroreceptor stimula-
tion in man does lower cardiac output, and also
decreases TPR (Carlsten, Folkow, Grimby, Ham-
berger, and Thulesius, 1958; Bevegird and Shep-
herd, 1966).
Arterial C 0 2 tension might also affect TPR, for
hypercapnia induced during wakefulness is associ-
ated withvasodilatation; however, the other changes
seen during hypercapnia-hypertension, tachy-
cardia, and increased cardiac output-do not re-
semble the changes seen in sleep. The effects of
hypercapnia on the resetting of the baroreflex in
awake man have recently been studied (Bristow,
Brown, Cunningham, Goode, Howson, and Sleight,
1968) and are of particular interest as the resetting
occurred in the opposite direction to that seen in
sleep (Fig. 7). Similar changes in blood gases
have been reported by Birchfield, Sieker, and Hey-
man (1958), although their pCOz levels were rather
higher than ours, both awake and asleep. Robin,
Whaley, Crump, and Travis (1958) showed that the
C 0 2 response curve is flattened, which they attri-
buted to a reduced sensitivity of the respiratory
centre during sleep. However, Fuleihan, Nakada,
Suero, Merrifield, Dutton, Permutt, and Riley
(1 963) using barbiturate-induced sleep, found no
difference in the transient responses to COz
breathing between sleep and wakefulness, although
Hypertensives
(n = 10)
- 11'7% (S.D. 5.2%)
-7.0% (S.D. 5.1%)
Inconstant fall
- 16.7% (S.D. 9.3%)
N o change
Variable change
+80 msec (S.D. 34 msec)
484 Bristow, Honour, Pickering, and Sleight
Subject No. 2
a 1 HYPERCAPNIA ACCOMPANYING SLEEP
Pulse Interval m sec.
160
140
ASLEEP
120
100
80
1 I I 1
Fig. 7. Effect of hypercapnia on baroreflex awake and asleep. The interrupted lines represent the resting
state, the solid lines hypercapnia. The resetting which occurs with sleep (left panel) is in the opposite
direction to that occurring when pC0, is raised without sleep (right panel).
the curves of pCOz versus ventilation rate were
shifted in the direction of a higher pCOz and lower
ventilation during sleep. These experiments are
similar in nature to our induced blood pressure
transients and, like them, might be interpreted on
the basis of a resetting of respiratory control during
sleep.
The haemodynamic differences between the two
groups of subjects, summarized in Table 3, are
quantitative rather than qualitative, the slightly
greater falls of arterial pressure in the hypertensives
being merely a reflection of their higher waking
levels, the percentage changes being very similar.
In the same way the greater baroreflex changes in
the normal subjects are paralleled by their higher
waking sensitivities. Thus the patient with hyper-
tension differs little from others in his circulatory
adjustments to sleep, except that he is still hyper-
tensive, and his baroreflex sensitivity usually re-
mains reduced.
Summary
Intra-arterial blood pressure, cardiac output,
arterial blood-gases and baroreflex changes (blood
pressure-heart rate reflex) have been studied in 19
Subject R.B.
b 1 INDUCED HYPERCAPNIA DURING
WAKEFULNESS
160
PaCq
56.4 mmHg
140
80
I I I I
subjects with normal and raised arterial pressure,
both awake and asleep. The blood pressure falls
during sleep, and the absolute fall is greater in
hypertensives, although the percentage changes are
similar (10%) in both groups.
Baroreflex sensitivity changes variably with sleep,
although in all five subjects so tested the sensitivity
was greater during REM sleep. Resetting of the
reflex, with a lower heart rate for a given systolic
pressure, was seen in 12 out of 15 subjects; these
changes were reversed on awakening. One subject
with autonomic denervation showed no resetting
and no changes in heart rate or blood pressure with
sleep.
There was no consistent change in cardiac output
in sleep for either group although peripheral
resistance fell significantly. PaCOz increased by
4 mm Hg during sleep and PaO, decreased by
5.4 mm Hg.
There does not appear to be any qualitative
difference between subjects with normal and high
blood pressures in their haemodynamic adjustments
during sleep except that the latter have an almost
five-fold reduction in baroreflex sensitivity both
awake and asleep.
 Cardiovascular Changes During Sleep
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