Download Arterial response during cold pressor test in borderline hypertension

Arterial response during cold pressor test
in borderline hypertension
A. B. LAFLECHE,1 B. M. PANNIER,2 B. LALOUX,1 AND M. E. SAFAR1
of Internal Medicine and Institut National de la Santé et de la Recherche Médicale
(U337), Broussais Hospital, 75014 Paris, and 2Manhès Hospital, Fleury-Merogis 91700, France
1Department
Lafleche, A. B., B. M. Pannier, B. Laloux, and M. E.
Safar. Arterial response during cold pressor test in borderline hypertension. Am. J. Physiol. 275 (Heart Circ. Physiol.
44): H409–H415, 1998.—We observed previously that sympathetic activation produced by lower body negative pressure
increases pulse-pressure amplification with little change in
mean pressure. Whether the cold pressor test (CPT) might
produce a similar hemodynamic pattern has been ignored.
Ten subjects with borderline hypertension and ten age- and
sex-matched normotensive controls were compared to investigate carotid-brachial pulse-pressure amplification (aplanation tonometry) and changes in brachial and carotid distensibility (echotracking technique) before and during CPT. The
maneuver markedly increased blood pressure without a
change in heart rate. Pulse-pressure amplification tended to
disappear as a consequence of a higher increase in carotid
than in brachial pulse pressure, due to an earlier return of
wave reflections at the carotid site. CPT caused a significant
decrease in carotid and brachial distensibility. Both results
were more pronounced in controls than in borderline hypertensives. Thus CPT reduces pulse-pressure amplification. In
humans, this change may greatly influence the calculation of
arterial distensibility, although this point is usually minimized in animal experiments. Furthermore, in young subjects, sympathetic stimulus may induce different arterial
responses, depending on the mechanism involved: reflex or
global nonspecific stimulus.
pulsatile arterial hemodynamics; wave reflection
THE BLOOD PRESSURE CURVE may be divided into two
components: a steady component, mean arterial pressure, and a pulsatile component, pulse pressure, which
is the difference between peak systolic and enddiastolic blood pressure (29). Whereas mean arterial
pressure remains almost constant along the arterial
tree, pulse pressure increases markedly from central to
peripheral arteries (15, 29). This is due to the changing
pattern in the timing of wave reflections when the blood
pressure propagates along arterial conduits with a
progressive decrease in lumen diameter and an increase in vascular rigidity. We have previously shown
(31) that the activation of the autonomic nervous
system produced by lower body negative pressure
(LBNP) is able not only to cause a slight decrease in
mean arterial pressure and a significant increase in
heart rate but also to enhance pulse-pressure amplification as a consequence of a substantial decrease in
central (carotid) pulse pressure with minimal changes
in peripheral (brachial) pulse pressure. However,
whether other maneuvers that activate the sympathetic nervous system may cause similar changes in
pulse-pressure amplification has never been investigated.
The cold pressor test (CPT) is known to cause a global
sympathetic activation in subjects with different levels
of baseline sympathetic tone, such as a group of normal
subjects and patients with borderline hypertension (23,
36). CPT results in a significant arteriolar vasoconstriction, with a subsequent increase in blood pressure and
a slight increase in plasma catecholamines but with no
change in heart rate (1, 5, 8, 32, 37). Associated changes
in the rigidity of large arterial vessels have been
observed (10), but, in normal volunteers, major discrepancies have been noted at the site of the radial artery
(3, 12). In particular, decreased or increased values of
distensibility and compliance have been obtained depending on the intensity of the stimulus and the
number of pulse-pressure measurements. Because distensibility is the ratio between pulsatile diameter and
pulsatile pressure, it is important to determine whether
the sympathetic activation produced by CPT is able to
substantially modify pulse pressure and greatly modify
pulse-pressure amplification.
In the present report, we investigated a population of
subjects with borderline hypertension in comparison
with a group of age- and sex-matched normotensive
controls. The goal of the study was twofold: 1) to
evaluate whether pulse-pressure amplification is modified by CPT, and 2) to determine the changes in arterial
diameter and distensibility at the site of two different
arteries, a peripheral, medium-sized muscular artery,
the brachial artery, and a central elastic artery, the
common carotid artery (9). In both cases, distensibility
was measured from local pulse pressure and pulsatile
diameter using a high-resolution echotracking technique.
METHODS
Patients. Ten Caucasian borderline hypertensive patients
(8 males, 2 females) ages 21–58 yr (33 6 13 yr, mean 6 SD)
and 10 normotensive subjects (7 males and 3 females) ages
28–45 yr (35 6 6 yr) were studied in the morning after they
had consumed a light, standardized breakfast in a temperature-controlled room (22 6 2°C). Normotension was defined
as auscultatory blood pressure ,140/90 mmHg measured at
three different times over a 2-wk period. Borderline hypertension (BHT) was defined as two casual blood pressure recordings with a diastolic blood pressure (DBP) $90 mmHg during
the previous 12 mo, plus at least two measurements with a
DBP ,90 mmHg (34). No patients had cardiovascular complication or other diseases. None of them had been previously
treated with cardiovascular agents. The principal clinical
characteristics of the subjects are given in Table 1. All of them
gave informed consent, and the study was approved by the
Ethical Committee of Broussais Hospital.
Description of study and CPT. Baseline conditions were
recorded after 20 min of rest in the supine position. Investiga-
0363-6135/98 $5.00 Copyright r 1998 the American Physiological Society
H409
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ARTERIES DURING CPT IN BORDERLINE HYPERTENSION
Table 1. Clinical characteristics
Weight, kg
Height, cm
Age, yr
SBP, mmHg
DBP, mmHg
Normal
BHT
P
72 6 8
175 6 11
35 6 6
116 6 11
72 6 9
77 6 20
175 6 9
33 6 13
146 6 7
84 6 7
NS
NS
NS
,0.001
,0.01
Values are means 6 SD for normal and borderline hypertensive
(BHT) subjects. Systolic (SBP) and diastolic blood pressure (DBP)
were measured with a sphygmomanometer. NS, not significant.
tions included brachial automatic blood pressure measurement every 2 min with a Dinamap apparatus (Critikon,
Chatenay-Malabry, France) on the left arm (homolateral to
the cold pressor stimulus), measurement of the right common
carotid artery geometry with an echotracking system, followed by measurement of the right carotid artery local pulse
pressure (PP) with the aplanation tonometry method, and
then, using the same methods, recordings of geometry and PP
at the right brachial artery at the level of the elbow, with the
upper limb maintained in an armrest.
The CPT was performed by immersing the left hand up to
the wrist in ice-cold water at 4°C for 5 min (37). All measurements were begun after 30 s of stimulus. Dinamap blood
pressure recordings were made every minute. Only one
recording of geometric and pressure measurements was made
at both arterial sites by two trained investigators simultaneously during the 5 min of stimulus, but all the arterial
measurements were finished at the beginning of the 5th
minute of Dinamap blood pressure recording.
PP and central arterial reflection wave measurement. The
carotid and radial PP were measured with a transcutaneous
aplanation tonometry system (Millar, Houston, TX) (13, 21,
22). Briefly, the carotid PP wave is recorded with a highfidelity strain-gauge transducer internally calibrated (1
mV 5 1 mmHg) with a preamplifier on a paper recorder at the
speed of 100 mm/s (Siemens, Saint Denis, France). The probe
is handheld and positioned at the level of the artery where the
signal is the best and most accurate in terms of shape and
amplitude. The use of this method requires training to obtain
accurate and adequate angulation between the probe and the
vessel axis, because transducer movements caused by movements of the patient or the operator’s hand or by inappropriate hold-down pressure can alter the quality of the recording,
as described by Kelly et al. (13). Validation of PP determination using simultaneous intra-arterial measurements has
been previously published in detail (1, 7).
This method also allows the analysis of the timing of wave
reflections by using the changes in the shape of the pressure
curve at the level of the carotid artery and ascending aorta
during the cardiac cycle (7). The aortic PP waveform has been
extensively described already and was generally shown as
manifesting an inflection point (Pi ) dividing the pressure
wave into an early and a mid-to-late systolic peak (7, 16, 19,
22, 31). This inflection point has been described as indicating
two different waveform components on the recorded pressure:
a forward, or incident, wave and a backward, or reflected,
wave. The mid-to-late systolic peak is interpreted as the
result of the reflected wave coming back from peripheral sites
of reflection and is responsible for a late increase in PP and
systolic blood pressure (SBP). The maximal peak (Pk ) of the
blood pressure curve is influenced by the timing and the
amplitude of this reflected wave. When the reflected wave is
attenuated and/or delayed, this wave will not contribute to
the maximal aortic systolic peak: Pk will happen early in
systole, Pi will appear after Pk, and (Pk 2 Pi ) will be expressed
conventionally as a negative value. In that case, (Pk 2 Pi ) is
only an indicator of the contribution of the reflected wave to
the late systolic pressure. In younger subjects, Pi may be
particularly difficult to evaluate during systole because the
reflected wave occurs during diastole after the aortic valve
closure. When the backward pressure is not attenuated
and/or delayed, the reflected wave will contribute to the aortic
peak SBP: Pk will happen later than Pi, and (Pk 2 Pi ) will be
expressed as a positive value, thus representing the amplification of PP and SBP due to the reflected wave. Finally, the ratio
of (Pk 2 Pi ) to PP (as a percentage), expressed conventionally
as a negative or a positive value, is considered a rough
indicator of the relative contribution of the reflected pressure
wave to the systolic pressure in central arteries, particularly
the ascending aorta. On the other hand, the delay from the
foot of the pressure wave to the Pi (Dtp ) has been interpreted
as representing the travel time for the incident wave to reach
the peripheral reflecting sites and return (16, 28). Left
ventricular ejection time (LVET) was measured from the foot
of the pressure wave to the diastolic incisura. Murgo et al.
(28) classified the aortic pressure waveform, depending on
age and hypertensive status, into three subgroups according
to its shape: type A, in which Pk occurs in late systole after a
well-defined Pi and (Pk 2 Pi )/PP . 0.12; type C, in which Pk
precedes Pi and (Pk 2 Pi )/PP , 0.0; and type B, which is the
same as type A except that 0.0 , (Pk 2 Pi )/PP , 0.12.
Typically, type A is observed in older subjects and hypertensive patients, and type C is observed in normotensive subjects
and younger subjects. SBP and PP may increase significantly
from central to peripheral arteries. This contrasts with drops
in DBP and mean blood pressure (MBP) from the ascending
aorta to the radial artery that do not exceed 1–2 mmHg (15,
29). Therefore, carotid SBP and PP were estimated from the
carotid pressure waveform, with the assumption that brachial and carotid DBP and MBP were equal, with the use of
the HP Sketch Pro Tablet Digitizer connected to a PC. Carotid
MBP was computed from a carotid pressure tracing from the
area of the carotid pressure waveform, determined from the
Tablet Digitizer, and was set equal to brachial MBP (21).
Repeatability of measurements has been previously reported
(31).
Pulsatile changes in arterial diameter measurement. The
artery diastolic diameter (Dd ) and its absolute and relative
changes during the systolic-diastolic periods [systolic diameter (Ds ) 2 Dd and (Ds 2 Dd )/Dd] were measured with a
high-fidelity vascular echotracking system (WTS, Maastricht, The Netherlands) (11, 14). Briefly, this apparatus
enabled us to assess transcutaneously the displacement of
the arterial walls during the cardiac cycle and, hence, the
time-dependent changes in arterial diameter relative to its
initial diameter at the beginning of the cardiac cycle. On the
basis of the two-dimensional B-mode image, an M-line was
selected perpendicular to the artery, the radiofrequency echographic signal of four to eight cardiac cycles was recorded
digitally, and a tracking system allowed the vessel walls to be
tracked during the whole cardiac cycles. Dd, (Ds 2 Dd ), and
(Ds 2 Dd )/Dd were automatically calculated in a few seconds
by the computer.
From these geometric and pressure variables, the distensibility coefficient (DC) and cross-sectional compliance (CSC)
were calculated. CSC is equal to [(Ds 2 Dd )/2PP]pDd, and DC
is [2(Ds 2 Dd )/Dd]/PP (4, 17, 31, 35). Repeatability of measurements has been described in detail elsewhere (31).
Statistical analysis. Results are expressed as means 6 SD.
The clinical characteristics of both groups were compared
with the use of a t-test for unpaired values (NCSS software,
Kaysville, UT). We analyzed the changes in blood pressure
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ARTERIES DURING CPT IN BORDERLINE HYPERTENSION
Table 2. Changes in blood pressure and heart rate during cold pressor test
Normal
SBP, mmHg
DBP, mmHg
MBP, mmHg
PP, mmHg
HR, beats/min
BHT
ANOVA
Baseline
CPT
Baseline
CPT
Group factor
CPT factor
Interaction
113 6 10
68 6 6
85 6 7
45 6 6
66 6 9
126 6 13
72 6 7
94 6 8
55 6 8
68 6 11
144 6 8
83 6 7
106 6 5
61 6 9
77 6 14
154 6 9
88 6 9
114 6 6
68 6 10
77 6 14
,0.001
,0.001
,0.001
,0.001
NS
,0.001
,0.05
,0.001
,0.001
NS
NS
NS
NS
NS
NS
Values are means 6 SD. CPT, cold pressor test; MBP, mean blood pressure; PP, pulse pressure; HR, heart rate.
and heart rate minute by minute throughout the CPT using a
two-way ANOVA for repeated measures (group, time). In case
of significant variations in the time factor, with no group-time
interaction, we subsequently performed a t-test at each
minute in comparison with the baseline value in each group of
patients. A two-way ANOVA for repeated measures (group,
test) was performed to analyze the changes in parameters
throughout the study. A group-test interaction was the indicator of the difference in behavior between the two groups.
Finally, a three-way ANOVA (group, test, arterial site; data
not shown) was performed to compare behavior during CPT
depending on the measured artery (carotid or brachial). A P
value , 0.05 was considered significant.
time of the reflection wave (Dtp ), the relative stroke
change in diameter [(Ds 2 Dd )/Dd], CSC, and DC. Although CSC seemed to decrease less in patients with
BHT (due to differences in diameter behavior), a grouptest interaction was only observed for carotid artery Ds
and Dd, which decreased in patients with BHT but
increased in normal controls (P , 0.05). The augmentation index [(Pk 2 Pi )/PP] increased more in normal subjects (interaction: P , 0.05) from a negative value to a
positive amplification, suggesting a different hemodynamic behavior between groups at the central artery
level.
RESULTS
Table 1 shows the clinical characteristics of both
groups of patients. Whereas body weight, height, and
age did not differ, the blood pressure measured with a
mercury sphygmomanometer significantly differed, although the mean value for DBP was only slightly
increased in subjects with borderline hypertension.
Table 2 shows the changes in mean values of blood
pressure and heart rate (automatically recorded with
Dinamap) during the CPT. All the variables of blood
pressure (SBP, DBP, MBP, and PP) were significantly
higher in patients with BHT (group factor: P , 0.001,
P , 0.001, P , 0.001, and P , 0.01, respectively). The
basal level of heart rate was higher in patients with
BHT than in normotensive subjects (P , 0.01). The
CPT increased all variables of blood pressure in both
groups (P , 0.001, P , 0.01, P , 0.001, and P , 0.001,
respectively), but heart rate did not change during
CPT. However, no group-time interaction was observed.
Figure 1 shows the SBP, DBP, PP, and heart rate
evolution during the CPT minute by minute. The group
factor was significantly different for blood pressure but
not for heart rate. The latter remained unchanged
throughout the test, whereas SBP increased from the
first minute until the end of the test. The same finding
was observed for PP, but only in normal subjects. DBP
also increased from the beginning of the stimulus but
returned to baseline after the 3rd minute. There was no
group-time interaction, suggesting a similar behavior
between groups.
Table 3 shows the hemodynamic changes observed
for the carotid artery. Between-group differences were
observed for local SBP, DBP, and PP (higher in patients
with BHT; P , 0.001, P , 0.01, and P , 0.01,
respectively) as well as CSC and DC (P , 0.05 and P ,
0.01, respectively). CPT increased local SBP, DBP, PP,
(Pk 2 Pi ), and (Pk 2 Pi )/PP and decreased the transit
Fig. 1. Kinetics of systolic (SBP) and diastolic blood pressure (DBP),
pulse pressure (PP), and heart rate during cold pressor test (CPT)
compared with baseline in normal subjects (s) and borderline
hypertensive (BHT) patients (r). NS, not significant. * P , 0.05;
** P , 0.01 vs. baseline. For each variable, interaction is not
significant.
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ARTERIES DURING CPT IN BORDERLINE HYPERTENSION
Table 3. Carotid artery changes in local pressure, diameter, compliance, distensibility, and reflection wave
Normal
Dd , mm
Ds , mm
Ds 2 Dd , µm
(Ds 2 Dd )/Dd , %
SBP, mmHg
DBP, mmHg
PP, mmHg
CSC, 1022 mm2/mmHg
DC, 1023 mm21
Pk 2 Pi , mmHg
(Pk 2 Pi )/PP, %
Dtp , ms
LVET, ms
Dtp /LVET, %
BHT
ANOVA
Baseline
CPT
Baseline
CPT
Group factor
CPT factor
Interaction
6.28 6 0.48
6.74 6 0.53
456 6 153
7.33 6 2.45
103 6 8
68 6 6
35 6 4
13.04 6 4.9
4.21 6 1.62
21.61 6 5.9
25.22 6 16.00
171 6 25
305 6 19
0.56 6 0.08
6.60 6 0.58
7.02 6 0.60
418 6 125
6.36 6 2.0
122 6 11
73 6 7
50 6 8
8.45 6 3.05
2.65 6 1.00
6.46 6 5.74
12.12 6 11.45
148 6 24
307 6 16
0.48 6 0.07
6.51 6 0.54
6.90 6 0.52
392 6 140
6.13 6 2.28
133 6 10
84 6 7
48 6 13
5.51 6 2.4
2.53 6 0.75
1.07 6 8.01
3.83 6 13.72
149 6 24
293 6 29
0.51 6 0.08
6.34 6 0.63
6.69 6 0.67
345 6 167
5.45 6 2.62
149 6 8
88 6 9
61 6 11
5.86 6 4.84
1.73 6 0.70
4.81 6 7.78
8.79 6 12.60
137 6 22
290 6 31
0.48 6 0.08
NS
NS
NS
NS
,0.001
,0.001
,0.01
,0.05
,0.01
NS
NS
NS
NS
NS
NS
NS
NS
,0.05
,0.001
,0.01
,0.001
,0.001
,0.001
,0.001
,0.001
,0.001
NS
,0.001
,0.05
,0.05
NS
NS
NS
NS
NS
NS
NS
NS
,0.05
NS
NS
NS
Values are means 6 SD. Dd and Ds , diastolic and systolic diameter, respectively; CSC, cross-sectional compliance; DC, distensibility
coefficient; Pk , maximal peak in blood pressure curve; Pi , inflection point in pressure wave; Dtp , delay to Pi representing transit time of wave
reflection; LVET, left ventricular ejection time.
Table 4 shows the hemodynamic changes observed
for the brachial artery. Between-group differences were
observed for local SBP, DBP, and PP (higher in patients
with BHT; P , 0.001, P , 0.001, and P , 0.05,
respectively). CPT increased local SBP, DBP, and PP
and decreased (Ds 2 Dd ), (Ds 2 Dd )/Dd, CSC, and DC.
For the two latter parameters, there was no group
effect. A group-test interaction was only observed for
(Ds 2 Dd )/Dd (P , 0.01) and for DC (P , 0.01), which
decreased less in patients with BHT.
The three-way ANOVA (data not shown) showed a
test-arterial site interaction only for locally measured
SBP (P , 0.02) with a smaller increase at the brachial
artery site.
Figure 2 shows the relative change (%) in DC,
arterial distension (Ds 2 Dd ), and local PP during the
CPT with respect to each group of patients and each
artery. The mechanism of the decrease in distensibility
involves a constant increase in PP, which is more
pronounced in normal subjects than in patients with
BHT. A decrease in arterial distension is also present
but is more pronounced in normal subjects, particularly
for the brachial artery.
In summary, CPT increased all the local pressures
and the timing of reflection waves in both groups and
decreased relative stroke change in diameter and arte-
rial distensibility at each arterial site. Intergroup
analysis showed that during the CPT, amplification of
reflection waves was higher in normal subjects than in
patients with BHT, with an increase in carotid diameters. Relative stroke change in brachial diameter and
brachial artery DC decreased more in normal subjects
than in patients with BHT. PP amplification, evaluated
from the ratio of brachial to carotid PP, decreased
markedly during CPT in both groups and reached
similar values during CPT (Fig. 3).
DISCUSSION
CPT is a classic test of sympathetic activity causing
arteriolar vasoconstriction, resulting in an increase in
blood pressure without a change in heart rate. In the
present study, we showed that CPT was responsible for
a disappearance of pulse pressure amplification as a
consequence of an earlier return of carotid wave reflections and an increase in carotid pulse pressure. Arterial
distensibility was reduced at the site of the radial and
carotid arteries, but a group effect was observed only
for the carotid artery. In addition, a lesser response was
noted in subjects with BHT than in controls.
CPT and pulse pressure amplification. During the
CPT, we have shown that blood pressure increased
Table 4. Brachial artery changes in blood pressure, diameter, compliance, and distensibility
Normal
Dd , mm
Ds , mm
Ds 2 Dd , µm
(Ds 2 Dd)/Dd , %
SBP, mmHg
DBP, mmHg
PP, mmHg
CSC, 1022 mm2/mmHg
DC, 1023 mm21
Values are means 6 SD.
BHT
ANOVA
Baseline
CPT
Baseline
CPT
Group factor
CPT factor
Interaction
3.39 6 0.75
3.68 6 0.78
286 6 191
8.8 6 6.6
116 6 10
66 6 6
50 6 10
3.32 6 2.36
3.87 6 3.24
3.60 6 0.73
3.70 6 0.75
171 6 103
4.9 6 3.3
122 6 11
75 6 6
55 6 10
1.86 6 1.10
1.86 6 1.20
4.08 6 0.93
4.28 6 0.95
209 6 173
5.1 6 4.1
145 6 8
85 6 6
59 6 9
2.20 6 1.60
1.70 6 1.30
4.20 6 0.95
4.35 6 0.91
152 6 96
4.0 6 3.0
154 6 4
90 6 7
66 6 8
1.46 6 0.84
1.24 6 0.98
NS
NS
NS
NS
,0.001
,0.001
,0.05
NS
NS
NS
NS
,0.001
0.001
,0.001
,0.001
,0.001
,0.001
,0.001
NS
NS
NS
,0.01
NS
NS
NS
NS
,0.01
ARTERIES DURING CPT IN BORDERLINE HYPERTENSION
Fig. 2. Relative changes in distensibility coefficient, arterial distension [systolic diameter (Ds ) minus diastolic diameter (Dd )], and local
PP in carotid (filled bars) and brachial arteries (open bars) in normal
subjects (A) and BHT patients (B) during CPT.
without a significant difference between groups. Although larger increases were found in several studies
including borderline hypertensive subjects (18, 24, 25),
the present finding has already been shown by other
groups (26, 27, 30). Such discrepancies could be explained mainly by methodological aspects, particularly
differences in duration of stimulus. However, even
when blood pressure was measured minute by minute,
we did not observe any difference in responses between
Fig. 3. Ratio of brachial PP (PPb ) to carotid artery PP (PPc ) in
baseline condition and during CPT in normal subjects (s) and BHT
patients (r); au, arbitrary units. P , 0.01, baseline vs. CPT.
H413
groups (see Fig. 1, interaction NS). SBP increased in
both groups throughout the stimulus in comparison
with baseline, except at the 5th minute of recording in
patients with BHT. With regard to DBP, the increase
was observed only until the 2nd minute in patients
with BHT and the 3rd minute in controls. However, this
small difference may be important to consider in terms
of calculation of pulse pressure, which increased in
normal subjects but not in patients with BHT. In
previous studies, differences in intensity of stimulus
and in the timing of measurements have been responsible for discrepancies in pulse-pressure calculations
and, hence, in compliance determinations of the radial
artery (3, 12). In this study, according to average values
or minute-by-minute recordings, heart rate did not
show any significant variation, as already reported by
others (1, 32, 37). Finally, one major limitation of this
study is related to the intermediate duration of hemodynamic changes observed during the 5-min CPT. However, even in patients with BHT, the increase in SBP
lasted until the beginning of the 5th minute of the test,
and our vascular examinations were always finished
during the first part of this 5th minute.
One of the major findings of this study is the behavior
of the aortic reflection waves during CPT. In normal
subjects, as expected (7, 19, 28), the shape of the
baseline carotid artery pressure curve was of type C,
whereas in patients with BHT, the baseline pressure
curve was of type A or B. Expressed in terms of the
augmentation index [(Pk 2 Pi )/PP] and the delay to Pi
(absolute Dtp, or relative to LVET), the differences did
not reach the statistically significant level. During
CPT, all the normal subjects presented a type B or A
central pressure curve, and the change in augmentation index was of higher amplitude than in patients
with BHT. It is well established that, for a given
absorption coefficient of the arterial tree, reflection
wave depends on two principal factors: the length of the
arterial tree, particularly until the reflection site(s),
and the velocity of the wave travel (28, 29). With regard
to the length of the arterial tree, the reflection site(s)
are considered as the embranchments (particularly at
the level of renal arteries) and bifurcation of the aorta
(16) and, mostly, the arteriolar network (20, 29), which
directly depends on the status of the arteriolar vasoconstriction. During CPT, as a consequence of the increase
in peripheral resistance, the arteriolar site of reflection
becomes closer to the heart and contributes to enhance
the impact of the backward wave on central pulse
pressure. On the other hand, it is well known that the
pulse-wave velocity is influenced not only by the arterial physical properties but also by the level of blood
pressure (29). Thus, due to the increase in blood
pressure observed during CPT, we can reasonably
assume that the pulse-wave velocity increased significantly and contributed to the enhancement of reflection
waves. Finally, the global effect of wave reflections in
both populations was a significant decrease in Dtp and
an increase in (Pk 2 Pi )/PP, indicating an earlier return
of the backward pressure wave and causing a higher
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ARTERIES DURING CPT IN BORDERLINE HYPERTENSION
carotid systolic peak, which was even more pronounced
in normal subjects than in patients with BHT.
Subsequently, the major finding in both populations
of subjects was the disappearance of pulse-pressure
amplification during CPT (Fig. 3). This hemodynamic
pattern is largely different from that observed during
the sympathetic activation produced by LBNP (31).
During LBNP, an increase in pulse-pressure amplification occurs because of a decrease in carotid pulse
pressure in relation to an acceleration of heart rate and
a shortening of LVET. During CPT, such a change was
totally absent, because there was no significant change
in heart rate.
Changes in compliance and distensibility under CPT.
Until recent years, in most studies in the literature,
compliance was evaluated in vitro from arterial segments on which a steady pressure was applied to
determine the static pressure-diameter curve (29). However, during such studies, when a sinusoidal transmural pressure could be applied acutely, it was possible to
determine dynamic compliance at different arbitrary
levels of steady transmural pressure (2). In a given
large artery, dynamic compliance is known to be constantly lower than the corresponding static compliance
because of the frequency dependence of the viscosity of
the arterial wall (2). Subsequently, when two arteries
were simultaneously studied and compared in vitro,
the same sinusoidal transmural pressure was applied
to determine the dynamic compliance of each artery.
This methodology is totally different from that of the
dynamic compliance measurements in clinical studies.
In a given subject, when two different arteries are
compared, this comparison is obviously done for the
same mean arterial pressure (which is constant along
the arterial tree) but at different values of pulse
pressure, because of the presence of pulse-pressure
amplification. Using this procedure, we showed that,
both before and during CPT, distensibility was reduced
in subjects with BHT, but only at the site of the carotid
artery, not at the site of the brachial artery. This finding
clearly demonstrates that changes in distensibility in
vivo are influenced not only by the level of blood
pressure but also by the changes in the intrinsic
properties of the arterial wall. In a previous study, we
compared in vitro the mechanical properties of the
muscular radial artery and the musculoelastic internal
mammary artery (6). We showed that under norepinephrine stimulation, the isobaric elastic modulus decreased in the former and was unchanged in the latter,
suggesting that the sympathetic response is influenced
by the baseline status of vascular structure and function. Other hypotheses may arise taking into account
the approach of integrative physiology. It is possible
that activation of thermoreceptors in the skin during
cold exposure sends afferent impulses to the central
nervous system, which, in turn, may cause the radial
artery (close to the skin) and the carotid artery (away
from the skin) to respond in a significantly different
manner, although this suggestion results from study of
the arteriolar splanchnic bed (33), not large arteries.
In the case of large arteries studied under physiological conditions, pulse pressure is known to be the
mechanical signal producing an increase in pulsatile
diameter. Thus it is expected that the higher the pulse
pressure, the higher the pulsatile change of diameter.
In contrast with this simple logic, we observed that
during CPT, the increase in pulse pressure was associated with a significant decrease (and not an increase) in
pulsatile diameter. Thus, with the activation of the
autonomic nervous system produced by CPT, both a
mechanical (increase in pulse pressure) and a nonmechanical (decrease in pulsatile diameter) alteration
were obtained. In normal subjects, the two mechanisms
contributed to the decrease in distensibility during
CPT, particularly for the brachial artery (Fig. 2). In
subjects with BHT, only the increase in pulse pressure
contributed to the decrease in distensibility, resulting
in a smaller change in arterial stiffness.
In conclusion, the present study has shown that the
interpretation of the distensibility changes of the large
arteries is quite different in situations of in vivo and in
vitro experiments. In humans the exact role of blood
pressure should be evaluated by taking into account
the presence of pulse-pressure amplification. Pulsepressure amplification tends to disappear during CPT
as a consequence of a higher increase in carotid than in
brachial pulse pressure. Such changes in normal subjects are different from those in patients with BHT,
possibly as a consequence of a higher basal sympathetic
tone in the latter.
Address for reprint requests: M. Safar, Médecine 1, Hôpital
Broussais, 96 rue Didot, 75014 Paris, France.
Received 14 November 1997; accepted in final form 10 April 1998.
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