Download Effects of the Cold Pressor Test on Muscle Sympathetic Nerve

Effects of the Cold Pressor Test on
Muscle Sympathetic Nerve Activity in Humans
RONALD G. VICTOR, WAYNE N. LEIMBACH, JR., DOUGLAS R. SEALS,
B. GUNNAR WALLJN, AND AlXYN L. MARK
With the research assistance of Joan Kempf
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SUMMARY The purpose of this study was to determine the effects of the cold pressor test on
sympathetic outflow with direct measurements of nerve traffic in conscious humans and to test the
strength of correlation between sympathetic nerve discharge and the changes in arterial pressure,
heart rate, and plasma norepinephrine. In 25 healthy subjects, arterial pressure, heart rate, and
muscle sympathetic nerve activity were measured with microelectrodes inserted percutaneously into a
peroneal muscle nerve fascicle in the leg during immersion of the hand in ice water for 2 minutes.
Arterial pressure rose steadily during the first and second minutes of the cold pressor test. Muscle
sympathetic activity (burst frequency x amplitude) did not increase in thefirst30 seconds of the test
but increased from 230 ± 27 to 386 ± 52 units (mean ± SE, p< 0.05) by the end of the first minute of
the test and to 574 ± 7 3 (p<0.01) during the second minute. In contrast, heart rate increased
maximally during thefirst30 seconds of the cold pressor test and returned to control during the second
minute. The increases in heart rate were abolished by /3-adrenergic blockade. The increases in muscle
sympathetic activity during the cold pressor test were correlated with the increases in both mean
arterial pressure (r=0.86, p<0.01) and peripheral venous norepinephrine (r=0.72, p<0.05);
however, large changes in nerve traffic were associated with small changes in plasma norepinephrine.
The major new conclusions from this study are that 1) stimulation of sympathetic neural outflow to
skeletal muscle is an important component of the sympathetic response to the cold pressor test, 2) the
cold pressor test appears to produce differentia] effects on sympathetic outflow to the heart and to the
skeletal muscles, and 3) the arterial pressure response to the cold pressor test provides an approximate
index of muscle sympathetic activity in this setting. (Hypertension 9: 429-436, 1987)
KEY WORDS • cold pressor test
norepinephrine
sympathetic nerve activity • heart rate • plasma
I
to evaluate sympathetic neural control of the peripheral
and coronary circulations in humans. The CPT has
been reported to produce exaggerated pressor responses in hypertension-prone persons2"7 and augmented coronary vasoconstrictor responses in patients
with ischemic heart disease.8"10 In contrast, cold pressor responses are impaired in patients with orthostatic
hypotension caused by efferent sympathetic failure."
Furthermore, in experimental studies of neurocirculatory regulation in humans, the CPT has been used as
a nonspecific stimulus to sympathetic neural outflow.1214 In both clinical and experimental settings,
the underlying assumption has been that the CPT
evokes generalized sympathetic activation.
The CPT, therefore, would be expected to markedly
stimulate neural release of norepinephrine. However,
increases in plasma norepinephrine levels during the
CPT have been inconsistent and often surprisingly
small and have shown little, if any, correlation with the
changes in arterial pressure and heart rate.13"23 These
N most healthy human subjects, cutaneous application of ice water, the cold pressor test (CPT),
increases arterial pressure, heart rate, and vascular resistance.' For many years, the CPT has been Used
From the Department of Medicine, the Cardiovascular Center,
and the Veterans Administration Medical Center, University of
Iowa College of Medicine, Iowa City, Iowa, and the Department
of Clinical Neurophysiology, Sahlgrenska Hospital, Goteborg,
Sweden.
Supported by Clinical Investigator Award (HL01362) to Dr. Victor from the National Heart, Lung, and Blood Institute (NHLBI), by
research grants HL24962 and HL14388 from the NHLBI, and by
research funds from the Veterans Administration.
A preliminary report of this work was presented at the annual
meeting of the American College of Cardiology in Anaheim, California, March, 1985 (abstract published in J Am Coll Cardiol
1985;5:415).
Address for reprints: Ronald G. Victor, M.D., Cardiology Division, Rm. H8.116, Department of Internal Medicine, University of
Texas Health Science Center at Dallas, 5323 Harry Hines Blvd.,
Dallas, TX 75235-9034.
Received January 29, 1986; accepted December 10, 1986.
429
430
HYPERTENSION
previous studies do not permit definitive conclusions
regarding effects of the CPT on sympathetic nerve
traffic since plasma norepinephrine levels are influenced by other factors besides central sympathetic
outflow.
In the present study, we recorded sympathetic nerve
traffic directly with microelectrodes inserted into a peroneal muscle nerve fascicle (microneurography) in
awake, unanesthetized human subjects. Nerve traffic
in the leg was recorded during immersion of the hand
in ice water (CPT). The purpose of this study was 1) to
examine effects of the CPT on muscle sympathetic
nerve activity (MSNA); 2) to determine if the CPT
produces parallel responses in arterial pressure, heart
rate, and muscle sympathetic outflow; and 3) to test the
strength of correlation between the sympathetic nerve
response and the changes in plasma norepinephrine.
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Subjects and Methods
Twenty-one men and four women (ages 18 to 30
years) participated in this study after providing written, informed consent. All subjects were normotensive
(supine blood pressures < 140/90 mm Hg), were taking no medications, and had no evidence of cardiopulmonary disease, based on history and physical examination at the time of the study. The studies were
approved by the institutional committee on human
investigation.
Measurements
All experiments were performed with the subjects
supine. Efferent MSN A in the leg, blood pressure, and
heart rate were recorded during immersion of the left
hand in ice water. Heart rate (electrocardiogram), respiration (pneumograph), and MSN A (microneurography) were recorded continuously on a Gould physiological recorder (Model 28OOS; Oxnard, CA, USA).
Respiration was monitored to detect inadvertent performance of a Valsalva maneuver or prolonged exhalation since these respiratory maneuvers markedly stimulate MSN A.24 No such maneuvers were detected
during the CPT. Blood pressure was measured by
sphygmomanometry in the right arm. In 10 experiments, 60 ml of blood was withdrawn from a right
forearm vein for plasma catecholamine determinations. Plasma venous norepinephrine was measured by
high performance liquid chromatography.23
Microneurography
Multiunit recordings of postganglionic sympathetic
nerve activity were obtained from a muscle nerve fascicle in the right peroneal nerve posterior to the fibular
head. 26 -" The recordings were made with tungsten microelectrodes 200 /u.m in diameter in the shaft, tapering
to an uninsulated tip of 1 to 5 fj.m.
A reference electrode was inserted subcutaneously 1
to 3 cm from the recording electrode. The electrodes
were connected to a preamplifier with a gain of 1000
and an amplifier with a gain of 50-fold. The neural
activity was then fed through a bandpass filter with a
VOL
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1987
bandwidth of 700 to 2000 Hz. For monitoring during
the experiment, the filtered neurogram was routed
through an amplitude discriminator to a storage oscilloscope and a loudspeaker. For recording and analysis,
the filtered neurogram was fed through a resistancecapacitance integrating network (time constant, 0.1
seconds) to obtain a mean voltage display of the neural
activity.
There were three criteria for an acceptable recording
of MSNA. First, weak electrical stimulation (1-3 V;
0.2 msec; 1 Hz) through the electrode in the peroneal
nerve elicited involuntary muscle contraction (muscle
nerve fascicle) but not paresthesias (cutaneous nerve
fascicle). Second, tapping or stretching the muscles or
tendons supplied by the impaled fascicle elicited afferent mechanoreceptor discharges, whereas stroking
skin in the distribution of the peroneal nerve did not
evoke afferent discharges. Third, the neurogram revealed spontaneous, intermittent, pulse-synchronous
bursts that increased during held expiration and Phases
2 and 3 of a Valsalva maneuver, characteristic of
MSNA. Evidence that such activity represents efferent
sympathetic activity has derived from earlier studies
and includes 1) interruption of the activity by local
nerve block proximal but not distal to the recording
site, 2) elimination of the activity by ganglionic blockade, and 3) conduction velocity approximating 1
m/sec.26'27 Neurograms that revealed spontaneous activity characteristic of cutaneous sympathetic activity
were not accepted. Inadvertent contraction of the leg
muscles adjacent to the recording electrode produces
electromyographic activity, which causes a sudden
rise in baseline noise level on the mean voltage neurogram and produces a characteristic repetitive firing that
is evident on both the filtered neurogram and the audio
display. These electromyographic artifacts were readily distinguished from sympathetic bursts. Resting
nerve activity was measured for 6 to 10 minutes before
the experiments were begun to ensure that a stable
baseline level of nerve activity had been obtained.
Cold Pressor Test
The CPT was performed by immersing the subject's
left hand up to the wrist in ice water for 2 minutes.
Subjects avoided isometric contraction and performance of a Valsalva maneuver or held expiration during the CPT. Measurements were obtained during control, intervention (CPT), and recovery for 2 minutes
each.
/3-Adrenergic Blockade
In nine experiments we used /3-adrenergic blockade
to examine sympathetic drive to the sinus node during
the CPT. Heart rate responses to the CPT were measured before and 15 minutes after intravenous infusion
of propranolol, 0.15 mg/kg.
Plasma Norepinephrine
In 10 experiments we obtained venous blood samples for norepinephrine from an indwelling cannula in
a right forearm vein. Ten-milliliter aliquots were with-
431
COLD PRESSOR TEST/Victor et al.
drawn during the last 30 seconds of each minute of
control, CPT, and recovery periods while we performed simultaneous measurements of nerve traffic,
heart rate, and arterial pressure. The samples were
collected in chilled, heparinized tubes and promptly
centrifuged at 4°C. Norepinephrine levels were assayed using high performance liquid chromatography23
with an electrochemical detector (SmithKline Bio-Science Laboratories, Van Nuys, CA, USA). This assay
was sensitive to 10 pg/nl with a coefficient of variation
of 10%.
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Data Analysis
The mean voltage neurogram, electrocardiogram,
and respiratory movements were recorded at a paper
speed of 5 mm/sec. Sympathetic bursts were identified
by inspection of the mean voltage neurogram and expressed as bursts per minute (burst frequency) and as
bursts per 100 heartbeats. The latter provided a heart
rate-independent measure of central sympathetic outflow. The amplitude of each burst was determined by
inspection and calculated using a light pen and digitizing tablet. Total MSNA was calculated as bursts per
minute X mean burst amplitude and expressed in arbitrary units. We have previously determined that the
intraobserver variability in identifying bursts is less
than 5% while interobserver variability is less than
10%.28
Mean arterial pressure was calculated as diastolic
pressure plus one third of pulse pressure. The measurements of blood pressure were obtained during the last
30 seconds of each minute. Values for MSNA and
heart rate were calculated as the mean for the first 30
seconds and for the entire first and second minute of
the CPT. For the comparisons of arterial pressure and
sympathetic nerve responses to the CPT, neurograms
were analyzed with the investigator blinded to the
changes in arterial pressure.
Statistical analysis was performed using analysis of
variance and the Bonferroni method for multiple comparisons.29 A p value below 0.05 was considered significant. Results are expressed as the mean ± SE.
TABLE 1. Responses to the Cold Pressor Test
Control period
Variable
2nd min
1st min
Mean arterial pressure (mm Hg) 94±2
63±2
Heart rate (beats/min)
Muscle sympathetic nerve
activity
Bursts/min
18±2
30±3
Bursts/100 heartbeats
Total activity (bursts/min x
mean burst amplitude)
242 ± 32
Results
Arterial pressure, heart rate, and MSNA all increased significantly during the CPT (Table 1; Figures
1 and 2). Heart rate peaked in the first 30 seconds of
the CPT and returned toward the control values during
the second minute (see Figure 2). In contrast, MSNA
peaked during the second minute. Total MSNA (burst
frequency X amplitude) increased from 230 ± 27 to
386 ± 52 units ( p < 0 . 0 5 ) during the first minute of the
CPT and to 574 ± 73 units (p< 0.0001 compared with
control) during the second minute (see Table 1). The
peak responses in arterial pressure also occurred in the
second minute of the CPT. MSNA and arterial pressure returned toward control values during the recovery period.
There was a significant positive correlation between
the increases in mean arterial pressure and the increases in total MSNA from rest to the second minute
of CPT (r = 0.86, p < 0 . 0 1 ; Figure 3). There was also
a statistically significant correlation between increases
in arterial pressure and sympathetic nerve responses
from rest to the first minute of CPT (r = 0.59,
p < 0.05). In contrast, there was no significant correlation between increases in heart rate and MSNA during
the first minute of the CPT (r = 0.02) or with respect to
peak responses (r = 0.07).
/3-Adrenergic blockade with propranolol decreased
resting heart rate from 57 ± 3 to 48 ± 2 beats/min
(p<0.05) and abolished the increases in heart rate
during the CPT ( p < 0 . 0 1 ; Figure 4). In contrast, resting values of mean arterial pressure were similar before and after propranolol (92 ± 2 vs 90 ± 4 mm Hg),
as were the maximal increases in arterial pressure during the CPT: + 20 ± 2 mm Hg before vs + 18 ± 2 mm
Hg after propranolol.
Unlike MSNA, plasma norepinephrine did not increase in the first minute of the CPT (Figure 5). There
was a small but significant (p<0.05) increase in plasma norepinephrine in the second minute of the test, but
the peak increase in norepinephrine occurred in the
first minute of the recovery period. Figure 5 shows a
positive correlation between the peak change in total
Cold pressor test
Recovery period
2nd mis
1st min
93±2
63±2
1st min
106±2*
70 ±3*
2nd min
113±2*
66 + 3
100±2*
62±2
95±2
62±2
17±2
28±3
24 ±2*
36 ±4*
32 ±3*
50 ±4*
26 ±2*
45 ±4*
20±2
34 + 4
421+52*
288 ± 38
386 + 52*
574 + 73*
230 ±27
Values are means ± SE for 25 subjects. Values for total muscle sympathetic nerve activity are expressed in arbitrary
units.
*p < 0.05, compared with control values.
432
HYPERTENSION
148/72
Arterial
Pressure (mmHg)
Peroneal
Neurogram
(MSNA)
17_0/90
117
57
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152/72
55
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Cold Pressor Test
Control
Recovery
IOKC
Arterial
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165/110
128
137/72
53
Peroneal
Neurogram
(MSNA)
ECG
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Control
CoW Pressor Test
R»cov«ry
FIGURE 1. Segments from original records in two subjects (A and B) of arterial pressure (systolic/diastolic,
mean), mean voltage neurogram of muscle sympathetic nerve activity (MSNA), and electrocardiogram (ECG).
Data represent the last 30 seconds of each 2 -minute measurement period. Subject A showed typical increases in
arterial pressure and MSNA during the cold pressor test. Subject B showed more dramatic responses in both
arterial pressure and nerve traffic, the latter represented by the striking increase in frequency and amplitude of the
neural bursts. These sympathoexcitatory responses provide direct evidence that the cold pressor test is a potent
reflex sympathetic stimulus.
MSNA and the peak change in plasma norepinephrine
in response to the CPT (r = 0.72, /?<0.05). However,
large changes in MSNA were associated with only
small changes in norepinephrine levels.
Discussion
Most previous studies of sympatheticresponsesto
the cold pressor test have employed indirect indices of
sympathetic nervous activity.15"25 In this study, we
used intraneural microelectrode recordings to provide
direct measurements of muscle sympathetic nerve discharge during cold pressor stimulation in conscious
humans. The findings provide direct evidence for increased sympathetic drive to skeletal muscle during the
CPT and demonstrate the complexrelationshipsbetween the changes in muscle sympathetic outflow, arterial pressure, heart rate, and plasma norepinephrine
during this stimulus.
Effects of the Cold Pressor Test on Muscle Sympathetic
Nerve Activity and Arterial Pressure
Under resting conditions, there is normally an inverse relationship between acute changes in arterial
pressure and MSNA.25 Thus, in humans sympathetic
outflow to muscle is inhibited during arterial systole
and occurs during spontaneous decreases in arterial
pressure. In addition, MSNA is inhibited by sudden
increases in carotid baroreceptor activity produced by
neck suction.30 These observations indicate that
MSNA is normally under arterial baroreceptor reflex
control; however, during the CPT, this inhibitory influence of the arterial baroreceptor reflex on sympathetic outflow was overridden, since the increases in
MSNA occurred in spite of substantial increases in
arterial pressure.
We found a positive correlation between the increases in MSNA and the increases in arterial pressure
during the CPT. This was an unexpected finding since
previous studies have shown no correlation between
changes in arterial pressure and MSNA during static
handgrip,28 during lower body negative pressure,31
during clonidine administration,32 or between resting
levels of arterial pressure and basal levels of MSNA in
normotensive and hypertensive subjects.33 In contrast,
there is a positive correlation between increased levels
of MSNA and arterial pressure in patients with the
Guillain-Barre' syndrome.34 The present correlation appears to indicate that activation of sympathetic vasoconstrictor outflow to skeletal muscle is an important
component of the pressor response to the CPT. These
findings lend support to the use of the arterial pressure
response to the CPT as an approximate index of sympathetic neural function in studies of hypertension.2"7
COLD PRESSOR TEST/Victor et al.
76
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*
HR
MAP
(rranHg)
(beats/ 85
irtn)
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MSNA 400
(units)
(burst*
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t
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MSNA
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CPT, CPT,
C,
Cj
AMSNA
AMAP (mm Hg)
FIGURE 3. Relationship between increases in mean arterial
pressure (MAP) and increases in total muscle sympathetic nerve
activity (MSNA) from resting values to the second minute of the
cold pressor test for 25 subjects. There was a linear correlation
(y = 11.5, x= -58; r = 0.86, p<0.01) between MAP and
MSNA responses.
CPT, CPT2
P.,
i
433
FIGURE 2. Effects of the cold pressor
test (CPT) on mean arterial pressure
(MAP), heart rate (HR), and muscle
sympathetic nerve activity (MSNA).
Nerve activity is expressed in total activity (units = burst frequency x amplitude) and in bursts per 100 heartbeats.
Measurements were taken during 2 minutes each of control (C,, C2), cold pressor test (CPT,, CPT2), and recovery
(R,, R2). Values are means ± SEfor 25
subjects. Asterisk indicates values significantly different (p<0.05)from control. The maximal rise in HR occurred
in the first minute of the CPT, whereas
the maximal response in MAP occurred
in the second minute when there was a
striking increase in sympathetic nerve
traffic.
Comparison of Effects of Cold Pressor Test on
Sympathetic Nerve Activity to Skin and Skeletal Muscle
Previous studies have used microneurography to examine effects of cutaneous cold stimulation on sympathetic activity in humans. Delius et al.24 found that
MSNA did not increase during brief application of ice
to the abdomen. The discrepancy between their results
and our findings of increased MSNA during the CPT
mostly likely relate to differences in the duration of the
cold stimulus (i.e., a few seconds vs 2 minutes). More
recently, Fagius and Blumberg35 reported that the CPT
produced abrupt increases in skin sympathetic activity.
In contrast to our study in which muscle sympathetic
activity increased only after the first 30 seconds of the
CPT, skin sympathetic activity in the median nerve
increased immediately upon immersion of the contralateral hand in ice water.35 This finding is not surprising since skin sympathetic activity is extremely responsive to noxious or arousal stimuli.23 In contrast,
MSNA does not increase and sometimes tends to decrease in response to arousal stimuli.23 Thus, the increases in MSNA in our study cannot be explained as a
nonspecific response to arousal.
76
Haart Rate
(beats/mln)
45
C2
CPT, CPT 2
Ft,
FIGURE 4. Effects offi-adrenergic blockade on heart rate responses to the cold pressor test. Data are means ± SEfor nine
subjects during 2 minutes each of control (C,, C2), cold pressor
test (CPT,, CPT2), and recovery (R,, R2) both before (•) and
after (o) propranolol, 0.15 mglkg i.v. Asterisk indicates values
that are significantly different (p< 0.05) from control. Propranolol lowered resting heart rate (p<0.05) and abolished
(p < 0.0001) the chronotropic response to the cold pressor test.
Contrasting Effects of Cold Pressor Stimulation on
Muscle Sympathetic Nerve Activity and Heart Rate:
Possible Mechanisms of Cold Pressor-Induced
Sympathetic Neural Activation
The increases in heart rate during the CPT appear to
be mediated by sympathetic activation rather than by
parasympathetic withdrawal, since these increases
were abolished by propranolol. In contrast to the pressor response, the magnitude of the chronotropic response did not correlate with the change in MSNA
during the CPT. This finding indicates that heart rate
cannot be used as a global index of sympathetic activation during this test. Furthermore, the temporal dissociation of heart rate and MSNA responses suggests
that sympathetic outflow to the heart (sinoatrial node)
434
HYPERTENSION
200
150
100
CPT,
CPT,
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P.ak
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(94)
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100
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1987
Comparison of Muscle Sympathetic Nerve Activity and
Plasma Norepinephrine Responses
Previous studies have used plasma norepinephrine
levels to assess sympathetic neural activation during
the CPT.13-23 Cuddy et al., 15 using a fluorometric assay, reported that the CPT did not produce significant
increases in plasma norepinephrine. Even with the use
of radioenzymatic catecholamine assays, some investigators have failed to detect significant changes in plasma norepinephrine during the CPT.16 Other investigators have reported that the CPT increases plasma
norepinephrine by amounts ranging from + 2 0 % , "
+ 23%, 17 +64%, 1 8 + 67%, 22 + 152%, 20 to +240%. 2 1
In addition, previous studies have shown little or no
correlation between the increases in norepinephrine
and in arterial pressure during cold pressor stimulation. 1 7 1 9 2 3 Thus, the CPT has been considered to
be a less reliable stress test of cardiovascular autonomic function than submaximal dynamic exercise, in
which hemodynamic responses are closely associated
with consistently large increases in plasma catecholamines.18
250
Plum* [NE]
(pg/mO
VOL
200
P a l k A T o t l l MSNA
FIGURE 5. Comparison of plasma norepinephrine (NE) and
muscle sympathetic nerve activity (MSNA) responses to the cold
pressor test. A. Simultaneous measurements of plasma NE
and MSNA in 10 subjects (mean ± SE; p<0.05 compared with
control) during 2 minutes each of control (C/, C2), cold pressor
test (CPT1, CPT2), and recovery (Rh R2). The increases in
plasma NE lagged behind the increases in MSNA by approximately 1 minute. B. Relationship between the peak responses
(percentage increase) in plasma NE and in total MSNA to the
cold pressor test in the 10 subjects. There was a significant
linear relationship between these variables (y = —0.15,
x = + 77; r = 0.72, p<0.05). However, large increases in
MSNA were associated with small changes in plasma NE.
and sympathetic outflow to skeletal muscle during the
CPT are governed by different mechanisms.
We suggest that the propranolol-dependent increases in heart rate during the CPT are related to the
sensation of pain, since pain and heart rate during the
CPT vary similarly as a function of water temperature,3* since maximal heart rate and pain responses
both occur in the first minute of stimulus with subsequent cold adaptation, 36 ' 37 and since heart rate and pain
during the CPT have been modified in parallel with
biofeedback.38 We speculate that activation of cutaneous afferents mediates the increases in MSNA, but
further studies are needed to determine the relative
contributions of central neural and peripheral reflex
mechanisms in determining sympathetic nerve discharge during the CPT.
It is important to consider the duration of the CPT in
the interpretation of the plasma norepinephrine responses. Stratton et al.18 found that norepinephrine
levels did not increase during the first 2 minutes of cold
pressor testing but did increase during continued application of the CPT for up to 6 minutes. We also observed a small but significant rise in plasma norepinephrine after 2 minutes of cold pressor testing. In
addition, we found a significant positive correlation
between the peak changes in plasma norepinephrine
and MSNA. The strength of this correlation is similar
to that reported between resting values of norepinephrine and MSNA in normal subjects39 and in patients
with congestive heart failure.40 In spite of this correlation, our findings suggest two limitations in the use of
plasma norepinephrine as an index of MSNA during
the CPT. First, the increases in norepinephrine in venous blood lag behind the increases in MSNA. Thus,
the maximal increase in plasma norepinephrine occurs
approximately 1 minute after the removal of the cold
pressor stimulus. This lag presumably reflects the time
required for spillover of norepinephrine from adrenergic nerve terminals and diffusion into the circulation.
Second, and more importantly, plasma norepinephrine
is an insensitive measure of MSNA; large changes in
MSNA during the CPT are associated with small
changes in norepinephrine. This is not surprising since
norepinephrine levels are influenced not only by
MSNA but also by plasma catecholamine clearance,
by prejunctional modulation of neurotransmitter release from adrenergic nerve terminals, and by regional
differences in sympathetic drive and norepinephrine
release in tissues other than skeletal muscle. Thus,
measurement of plasma norepinephrine, especially
from blood drawn during the first or second minutes of
the cold pressor stimulus, would be expected to markedly underestimate the peak response in MSNA.
COLD PRESSOR JEST/Victor et al.
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Limitations of the Present Study and Possible Clinical
Implications
In conclusion, this study indicates that the CPT in
healthy humans is a potent stimulus to MSNA but
appears to exert differential effects on sympathetic outflow to the heart and skeletal muscles. The mechanisms responsible for the dissociation between the increases in MSNA and the propranolol-dependent
increases in heart rate were not elucidated in the present study. The findings in healthy subjects suggest that
in the clinical setting increases in cardiac sympathetic
activity should be reflected by the heart rate response
in the first 30 seconds of the test, whereas increases
in skeletal muscle sympathetic activity should be estimated by measuring the increases in arterial pressure in
the second minute of the cold pressor stimulus. Further studies are needed to determine if sympathetic
nerve responses to the CPT are altered in patients with
hypertension.
15.
16.
17.
18.
19.
20.
21.
22.
Acknowledgments
The authors thank Christine Sinkey for technical assistance and
Sara Jedlicka for secretarial assistance.
23.
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Effects of the cold pressor test on muscle sympathetic nerve activity in humans.
R G Victor, W N Leimbach, Jr, D R Seals, B G Wallin and A L Mark
Hypertension. 1987;9:429-436
doi: 10.1161/01.HYP.9.5.429
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