Clinical and Experimental Hypertension. Part A: Theory and Practice
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Cigarette Smoking and the Adrenergic Nervous System G. Grassi, G. Seravalle, D. A. Calhoun, G. Bolla & G. Mancia To cite this article: G. Grassi, G. Seravalle, D. A. Calhoun, G. Bolla & G. Mancia (1992) Cigarette Smoking and the Adrenergic Nervous System, Clinical and Experimental Hypertension. Part A: Theory and Practice, 14:1-2, 251-260, DOI: 10.3109/10641969209036186 To link to this article: http://dx.doi.org/10.3109/10641969209036186
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Date: 27 October 2015, At: 00:17
CLIN. AND EXPER. HYPER.-THEORY AND PRACTICE, A14(1&2),
251-260 (1992)
CIGARETTE SMOKING AND THE ADRENERGIC NERVOUS SYSTEM G.Grassi, G.Seravalle, D.A.Calhoun, G.Bolla and G.Mancia
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Cattedra di Semeiotica Medica, Istituto di Clinica Medica Generale e Terapia Medica, Universita’ di Milano, Centro di Fisiologia Clinica e Ipertensione, Milano, Italy Key Words: smoking, blood pressure, sympathetic nervous system, plasma catecholamines, rnicroneurography, sympathetic nerve activity
ABSTRACT The acute increase in blood pressure and heart rate that accompanies cigarette smoking is associated with a rise in plasma catecholamines and it is thus believed to result from stimulation of the adrenergic nervous system. We have employed direct recording of efferent post-ganglionic sympathetic nerve activity by the microneurographic technique from the peroneal nerve to determine whether this stimulation occurs centrally or peripherally. It was shown that during cigarette smoking blood pressure, heart rate, plasma norepinephrine and epinephrine do increase markedly. Sympathetic nerve activity, however, shows a concomitant specular reduction. Thus peripheral (adrenal gland stimulation, reduction in norepinephrine reuptake, reduction in catecholamine clearance, etc.) rather than central mechanisms explain the adrenergic involvement in the acute hemodynamic effect of smoking, the central sympathetic drive being inhibited rather than excited probably as a result of arterial baroreceptor stimulation.
INTRODUCTION Cigarette smoking acute blood
is associated with
tachycardia and
an
pressure rise (1) and we have recently shown that
these effects are so prolonged that during
repeated cigarette
smoking blood pressure and heart rate can be permanently elevated (2).
This paper
focuses on the adrenergic mechanisms responsible
for these changes.
251 Copyri@t 0 1992 by Marcel Dekker, Inc.
252
GRASS1 ET AL.
ACUTE PRESSOR EFFECTS Cigarette and
SMOKING
smoking acutely induces an increase
in systolic
diastolic blood pressure (1). This acute pressor effect has
an early onset (within one minute), it may average even 10-15% of pre-smoking blood
pressure values and is accounted
for by
an
increase in both cardiac output (due to a marked tachycardia) and systemic vascular resistance (2,3). Downloaded by [University of Otago] at 00:17 27 October 2015
Repeated pressor
smoking is not associated with an
effect of the first cigarette. This has been
shown by
recently
our group (2,4) in 10 normotensive smokers, who were
to smoke four cigarettes
asked
attenuation of
(each containing a nicotine
concentration of 1.1 mg) at the rate of one every 15 min.,
while
blood pressure was measured beat-to-beat by a non invasive finger device
and heart
rate was
assessed by
a
cardiotachometer
triggered by the R-wave on an ECG lead. As
shown in Figure 1, the first cigarette markedly increased
systolic blood pressure, diastolic blood pressure and heart rate. Similar peak blood pressure and heart rate values were for the
observed
other three cigarettes. In eachinstance, however, the
responses were so prolonged that blood pressure and
heart
rate
values remained elevated throughout. In the group as a whole
the
hourly increase in systolic and diastolic blood pressure amounted to 20.852.8 mmHg (mean+SEM) and 7.422.1 mmHg respectively, while the hourly increase in heart rate amounted to 18.252.6 beats/min. Thus
habitual cigarette smoking
is accompanied by
a
persistent blood pressure rise, and no short-term tolerance to the pressor effects of smoking occurs.
NEURAL MECHANISMS INVOLVED IN THE PRESSOR EFFECT OF SMOKING A
blood
large body of evidence suggests that smoking
increases
pressure through an activation of the sympathetic nervous
system (1,5,6). For example, nicotine is well known stimulant of sympathetic ganglia, and
its administration in
experimental
100-
110-
120-
130-
f 4th
T
-.. 70-
60-
5040-
6050-
40-
30-
J
80-
..
70-
80
(C)
Systolic blood pressure (a), diastolic blood pressure (b) and heart rate (c) before and during the peak effect of smoking a cigarette. Four cigarettes were smoked over 1 hour, one every 15 min. Data are shown as means (+SEM) from 10 normotensive smokers (from Ref. 2, by permission).
T
.. -
Figure 1
..
mmng
(b)
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VI
N UI W
z M
0
cj
z 0
H
x
3: 0
GRASS1 ET AL.
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2 54
0 Z
,
0
5
1 L
150r
-
Q,
w
-1 0
0
10
20
30
MINUTES Figure
2
Plasma norepinephrine and epinephrine levels during cigarette smoking (closed symbols) and sham-smoking (open symbols). The arrows indicate the smoking period (from Ref. 1, by permission).
animals has system
(7,8).
direct excitatory effects on the central nervous Furthermore, in humans cigarette smoking elicits a
marked increase in plasma norepinephrine. Finally, plasma circumstance.
This
epinephrine is also increased under is shown in Figure
2,
which
this
further
255
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SMOKING AND SYMPATHETIC TONE
Figure 3
Effect of i.v. infusion of a ganglionic blocking drug (trimethaphan) on sympathetic nerve activity (upper tracing) and arterial blood pressure (lower tracing) (from Ref. 10, by permission).
illustrates that the increase in plasma catecholamines associated with
smoking
is long-lasting, thus parallelling
the prolonged
blood pressure and heart rate responses. However, the provide
data based on plasma
conclusive
responsible
for a
sympathetic nervous central
catecholamines do
information on whether in man central
or peripheral
smoking
activation
system. As mentioned above nicotine
effect, but it is indeed possible that the
not
of
is the
has
increase
a in
plasma norepinephrine levels reported during smoking results from a
reduction
in the tissue clearance of
this neurotransmitter
2 56
CRASS1 ET AL.
and/or from a decrease in norepinephrine reuptake from adrenergic nerve terminals. In
two Swedish investigators, Hagbarth
1968
developed
and
a method for directly assessing intraneural
Vallbo,
recording
of efferent post-ganglionic muscle sympathetic nerve activity humans (200
(9).
tungsten microelectrodes
microm in the shaft) inserted percutaneously into peripheral (radial or peroneal) and adjusted
nerves Downloaded by [University of Otago] at 00:17 27 October 2015
The recording is made by
in
multiunit potentials That
these
until
characteristic
from sympathetic nerve fibers are
potentials represent
efferent
found.
post-ganglionic
sympathetic nerve traffic is proved by the following evidences. One, these potentials are eliminated by
pharmacological nerve
block proximal but not distal to the recording site (9,lO). TWO, the conduction velocity of the recorded spikes is approximately 1 m/sec.,
i.e.
the
same found for sympathetic C
nerve
fibers
(9,lO). Three, the recorded activity can be reversibly eliminated
by ganglionic blockade. This evidence is illustrated in Figure
3,
which
is taken from a paper of Delius and Wallin
is
clear
that the ganglion blocking drug, Trimethaphan,
induced
blood
pressure fall and that this was accompanied by
a
reduction of the neural activity, which was virtually after
It
(10).
15 min. from starting the drug administration.
infusion was stopped the neural activity regained
a
gradual
abolished After
the
its original
magnitude and pattern. There are several major advantages in the microneurographic approach as compared to the plasma
norepinephrine one
(11).
Microneurography allows to directly quantify sympathetic activity (number
over
time and
amplitude of
norepinephrine depends both
burst),
on release and
on
while
plasma
clearance and
reuptake at the level of the adrenergic nerve terminals, thereby representing
an
indirect
(and less
sensitive)
sympathetic drive. Microneurography also allows to
index
of
investigate
sympathetic stimuli so brief as to be hardly reflected by changes
257
SMOKING AND SYMPATHETIC TONE
Table 1 Hemodynamic, humoral and sympathetic nerve activity control and cigarette smoking in 9 subjects CONTROL
SMOKING
(mmHg)
13955.3
15724.8
Diastolic Blood Pressure (mmHg)
7654.7
8555.0
Heart Rate
(b/min)
6251.6
7923.7
Plasma Norepinephrine
(pg/ml)
243252.5
323257.1
Plasma Epinephrine
(pg/ml)
2528.6
Systolic Blood Pressre
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during
Muscle Sympathetic Nerve Activity (Units/min)
47211.5
24223 1
**
164227
Values are shown as means5SEM. Asterisks refer significance between smoking and control values.
to
**
** ** ** ** **
statistical p