Download Acute Depressor Effect of Alcohol in Patients With Essential

219
Acute Depressor Effect of Alcohol in Patients
With Essential Hypertension
Yuhei Kawano, Hitoshi Abe, Shunichi Kojima, Terunao Ashida, Kaoru Yoshida,
Masahito Imanishi, Hiroki Yoshimi, Genjiro Kimura, Mono Kuramochi, and Teruo Omae
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To investigate the time course of the effects of alcohol on blood pressure, we studied the response of
ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of
alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who
were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they
ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic
beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the
alcohol intake period than in the control period (125±3/74±2 versus 132±4/78±2 mm Hg,p<0.05), and
the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the
next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was
associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular
resistance as determined by echocardiography. Plasma catecholamlne levels and renin activity rose
significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day.
Blood glucose and serum insulin levels were comparable between the two periods. Three patients with
marked alcohol-induced flush had greater hypotensive and tachycardic responses than those who did not
show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively
correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results
indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic
vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for
assessing blood pressure in habitual drinkers. (Hypertension 1992;2<h219-226)
KEY WORDS • alcohol drinking • blood pressure monitoring, ambulatory • hemodynamics •
catecholamines • electrolytes • hypertension, essential
T
he relation between alcohol and hypertension is
well known. A positive association between the
level of habitual alcohol intake and blood pressure has been shown in many reports,1"5 and this
relation has been observed in whites, blacks, and
Asians. It has also been reported that abstinence from
alcohol results in a decrease of blood pressure in
drinkers.6-9
However, these observations depended on casual
blood pressure measurements taken in the daytime,
while most habitual drinkers consume alcohol in the
evening and at night. Alcohol has an acute vasodilatory
action,1011 and it has been our experience that many
hypertensive patients note a decrease in their blood
pressure after alcohol ingestion at home. It has been
recommended that the relation between the time of the
last alcohol intake and that of blood pressure measurement should be considered,2 but this has generally been
ignored. Inconsistent results have been reported about
From the Division of Hypertension and Nephrology, National
Cardiovascular Center, Suita, Osaka, Japan.
Supported by Research Grant for Cardiovascular Diseases
63C-2 from the Ministry of Health and Welfare.
Address for correspondence: Yuhei Kawano, MD, Division of
Hypertension and Nephrology, National Cardiovascular Center,
5-7-1 Fujishirodai, Suita, Osaka 565, Japan.
Received September 19, 1991; accepted in revised form April 2,
1992.
the acute effect of alcohol on blood pressure,12"22 but
most of these studies were carried out under conditions
unrelated to normal drinking patterns and had a relatively short observation period.
Ambulatory blood pressure monitoring is now widely
accepted as a useful method for the evaluation of
hypertensive subjects because it provides multiple blood
pressure recordings during the whole day and eliminates the observer's bias and the "white coat" effect on
blood pressure.23-24 In the present study, we examined
the effect of a single moderate dose of alcohol on the
ambulatory blood pressure in hypertensive patients
under standardized conditions that were designed to
mimic the usual drinking pattern. We also studied the
effects of alcohol on neurohumoral variables and hemodynamics in the same patients.
Methods
Subjects
Sixteen Japanese men with hypertension who were
habitual drinkers participated in this study. Informed
consent was given by each patient, and the study protocol was approved by the Ethics Committee of the
National Cardiovascular Center. All the patients were
diagnosed as having mild-to-moderate essential hypertension (average diastolic blood pressure, 90-114
mm Hg) after routine examinations at the Hypertension
220
Hypertension
Vol 20, No 2 August 1992
TABLE 1. Clinical Characteristics of the Sixteen Male Patients
With Essential Hypertension
Variables
Age (yr)
Height (cm)
Weight (kg)
SBP (mm Hg)
DBP (mm Hg)
Alcohol (ml)
55.2±3.3
165.5±1.2
65.2±2.2
159.5±4.7
91J±3.0
70.3 ±7.8
SBP, systolic blood pressure on admission; DBP, diastolic blood
pressure on admission; alcohol, amount of daily ethanol intake
before admission.
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Clinic of our institute. No patient had serious cardiac,
neurological, or hepatic disorders.
Table 1 shows the clinical characteristics of the 16
patients. They were from 22 to 70 years old (55.2±3.3
years, mean±SEM), and their daily alcohol intake
ranged from 15 to 150 ml (70.3 ±7.8 ml). Alcohol was
forbidden for at least 7 days before the study. Six
patients had never been treated for hypertension and
the remaining 10 patients were asked to discontinue
their antihypertensive medication for at least 7 days
before the study.
Protocol
All the patients were admitted to the National Cardiovascular Center Hospital where they consumed a
standard daily diet of 6,300 kJ (1,500 kcal) that contained 7-9 g NaCl. After 3-5 days of acclimatization,
the study was carried out in a randomized crossover
manner. Nine patients ingested alcohol first, and the
remaining seven patients ingested a control drink first.
On the alcohol intake day, each patient ingested 1 ml/kg
ethanol (as vodka with lime juice and water) with dinner
from 5:00 to 5:30 PM. On the control day, they consumed
a nonalcoholic beverage (lime juice and water) with the
evening meal. The two study periods were separated by
a rest day.
Noninvasive ambulatory blood pressure monitoring
was started at 4 PM on the alcohol intake and control
days. Echocardiography and subsequent venous blood
sampling were performed before dinner (4:30-5:00 PM)
and 90-120 minutes after the evening meal (6:30-7:00
PM). Blood pressure was also measured just before
blood collection (with the patient in the supine position)
and after the patient had been standing for 2 minutes.
Additional venous blood samples were collected at 60
minutes after supper (6 PM) and at 8 AM the next
morning.
Measurements
Ambulatory blood pressure and heart rate were measured every 30 minutes until noon the next day by an
oscillometric method using ABPM 630 recorders (Nippon Colin, Komaki, Aichi, Japan). This device uses a
silent cuff inflation system operated by compressed CO2
gas.25 The accuracy of each recorder was checked by
simultaneous measurement with a mercury sphygmomanometer, and all recorders showed a difference of
less than 10 mm Hg. The same recorder was used for the
alcohol intake and control days in each individual
1H
f
e
1
1
no
1*
10
0
4
f
11
Tim* of Day
FIGURE 1. Line graph shows ambulatory blood pressure at
30-minute intervals during the alcohol intake day (•) and the
control day (o) in 13 patients with essential hypertension.
subject. For analysis of the ambulatory blood pressure,
every 2-hour segment of the record was averaged.
M-mode echocardiograms were recorded at an equivalent paper speed of 50 mm/sec with two-dimensional
monitoring using a phased-array ultrasonic sector scanner and a 2.5 or 3.5 MHz transducer (model 77020A,
Hewlett-Packard, Waltham, Mass.). The patients were
in a partial left lateral decubitus position when they
were examined, and special attention was taken to avoid
misleading angulation of the left ventricular long axis in
relation to the ultrasound beam.26 All echocardiograms
were taken by an experienced examiner and were read
independently by two investigators. Left ventricular
dimensions and wall thickness were measured using the
leading edge technique, according to the recommendation of the American Society of Echocardiography.27
Left ventricular volumes were estimated by the cubefunction formula from the end-diastolic and end-systolic
left ventricular internal dimensions and were used to
estimate the stroke volume and cardiac output.28
Serum electrolyte and total protein levels as well as
the blood glucose were determined using a biochemical
analysis system (TBA-80S, Toshiba, Tokyo). Hematocrit was measured by a micTohematocrit method.
Plasma levels of renin activity (PRA), aldosterone, and
vasopressin, as well as serum levels of cortisol and
insulin were determined by radioimmunoassay. Plasma
catecholamines were assayed by high-performance liquid chromatography and trihydroxyindole fluorometry.
Data Analysis
All results are expressed as the mean±SEM. Data
were analyzed using repeated-measures analysis of variance with Fisher's test. Student's t test was used for the
comparison of two groups. Linear regression analysis and
stepwise regression analysis were used for the evaluation
of relations between the measured variables. A value of
/?<0.05 was considered statistically significant.
Results
Figure 1 shows the time course of ambulatory blood
pressure at 30-minute intervals, and Figure 2 shows
2-hourly means of ambulatory blood pressure and heart
rate from 4 PM to noon of the next day in 13 of the 16
hypertensive patients. Data for three patients were
Kawano et al
Depressor Effect of Alcohol
221
120
i no
m 100
-**
90
80
§0J
1
I
1
IT
It
11
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1
1
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T I M O ! Oiy
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1
70
II
.o
ThmolDay
FIGURE 2. Line graphs show ambulatory blood pressure
(upper panel) and heart rate (lower panel) expressed as
2-hourty means during the alcohol intake day (•) and the
control day (o). *p<0.05 between the two periods.
excluded because the ambulatory recordings were not
available for the entire period. Systolic and diastolic
blood pressure in the evening hours of the alcohol
intake day were significantly lower than those on the
control day. The hypotensive effect of alcohol was most
prominent at 3-4 hours after its intake (alcohol day,
115.8±3.0/68.5±2.1 mm Hg; control day, 139.4±4.6/
80.3 ±2.9 mm Hg,/?<0.05) and lasted for up to 8 and 4
hours for systolic and diastolic blood pressure, respectively. Heart rate reciprocally increased for 8 hours after
alcohol ingestion. Blood pressure and heart rate were
similar in the early and late morning of the next day
after both the alcohol and control days.
The average 20-hour ambulatory blood pressure in
the alcohol period was also lower than that in the
control period (systolic blood pressure, 124.8±2.5 versus 131.9+3.5 mm Hg,/><0.01; diastolic blood pressure,
73.7±1.8 versus 77.6±2.4 mm Hg,/?<0.05). Mean ambulatory blood pressure values for the individual subjects are shown in Figure 3. Eleven of the 13 patients
showed a reduction in mean blood pressure during the
alcohol period. The average heart rate was significantly
higher in the alcohol period than in the control period
(64.8+2.4 versus 58.7+1.9 beats per minute, /><0.01).
The hypotensive effect of alcohol was evident regardless
of the order of the alcohol and the control periods
(Table 2).
Control
Alcohol
FIGURE 3. Line plot shows mean 20-hour ambulatory blood
pressure during the alcohol intake and control days in hypertensive patients. MBP, mean blood pressure. **p<0.01 between the two periods.
Figure 4 shows neurohormonal variables for the 16
patients at 5 PM (before dinner), at 7 PM (after dinner),
and at 8 AM the next day (before breakfast). There were
no differences in plasma norepinephrine, epinephrine,
PRA, aldosterone, vasopressin, and serum cortisol between the alcohol intake and control days at 5 PM. After
alcohol ingestion (7 PM), the norepinephrine, epinephrine, and PRA levels were elevated significantly (norepinephrine, 412±58 versus 295±29 pg/ml; epinephrine, 51±14 versus 25±5 pg/ml; PRA, 3.1±0.7 versus
1.9±0.4 ng/ml/hr, alcohol intake versus control days),
whereas the vasopressin level was reduced (0.6 ±0.1
versus 1.1 ±0.2 pg/ml). A significant decrease in plasma
epinephrine level was noted after dinner on the control
day. By the next morning, there were no differences in
the measured variables. Serum cortisol levels showed
their normal circadian changes in both periods.
Serum sodium levels were comparable between the
alcohol intake and control days (Figure 5), but the
serum potassium level decreased after alcohol intake
(3.58±0.06 versus 3.98±0.06 at 7 PM, p<0.05). Serum
protein and hematocrit tended to be higher on the
alcohol intake day at 7 PM, although the difference was
not significant.
Blood glucose and serum insulin levels were determined at 5 PM, 6 PM, and 7 PM in 10 patients (Table 3).
These levels before and after dinner were not different
between the alcohol intake and control days. The blood
ethanol level at 7 PM on the alcohol intake day ranged
TABLE 2. Mean 20-Hour Ambulatory Blood Pressure Daring
the Alcohol Intake and the Control Days in Patients Who Took
the Alcohol Drink First (Group 1) and Those Who Took the
Control Drink First (Group 2)
Variables
Group 1 (n=7)
SBP (mm Hg)
DBP (mm Hg)
Group 2 (n=6)
SBP (mm Hg)
DBP (mm Hg)
Control day
Alcohol intake day
134±4
80±3
127±3'
76±3'
129±5
76±2
122±4*
72±2*
SBP, systolic blood pressure; DBP, diastolic blood pressure.
*p<0.05 vs. the control day.
222
Hypertension
Vol 20, No 2 August 1992
D Control
0 Alcohol
P<0 0i
500
t
S 250
LJ
Z
0
17
i
f
•—• 5
o
<
17
100
1§
S
n
DO
f"
50
LJ
0
19
o
17
1
~ 20
P< 0 05
19
17
19
I
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0.
FIGURE 4. Bar graphs show plasma levels of various hormones at 5 PM (before dinner), 7 PM (after dinner), and 8 AM
(next morning) on the alcohol intake and control days. NE,
norepinephrine; E, epinephrine; PRA, plasma renin activity;
Aldo, aldosterone; Cort, cortisol; VP, vasopressin. *p<0.05
vs. 5 PM.
from 0.6 to 0.9 mg/ml (0.7±0.1 mg/ml), which is considered to be within the range that produces mild ethanol
intoxication.
Reliable echocardiographic records were obtained in
eight patients. Resting hemodynamic variables before
dinner were similar in the two periods (Table 4). The
decrease in blood pressure and increase in heart rate
after alcohol intake were associated with a significant
increase in the cardiac index and a large decrease in the
peripheral vascular resistance. An increase in left ventricular fractional shortening and a decrease in left
• Control
0 Alcohol
145
1
140
135
17
6
19
5
17
19
1 1
.T*
17
19
45
P<OOJ
I «
40
17
19
8
35
Blood Glucose and Serum Insulin Levels on the Alco-
hol Intake and Control Days in Ten Hypertensive Patients
Variables
10
19
TABLE 3.
8
FIGURE 5. Bar graphs show serum sodium (Na), potassium
(K), and protein (Prot) levels and hematocrit (Ht) on the
alcohol intake and control days.
Glucose (mg/dl)
Control
Alcohol
Insulin (microunits/ml)
Control
Alcohol
5 PM
6 PM
7 PM
91.1±1.8
90.4±1.7
144 5 ±9.6
131,0±8.5
120.0±3.8
113.9±4.7
12.2±2.6
9.8 ±3.0
43.7±5.4
40.7±7.1
36.6±5.8
41.2±4.7
ventricular end-systolic wall stress were also observed in
the alcohol intake period.
The change in mean blood pressure induced by
alcohol intake (mean blood pressure at 7 PM minus
mean blood pressure at 5 PM) correlated positively with
the mean blood pressure before drinking, the age, and
the change in plasma norepinephrine (Figures 6 and 7).
The relation between the change in mean blood pressure and the baseline blood pressure or the variation in
norepinephrine was also significant by stepwise regression analysis. The change in mean blood pressure did
not correlate significantly with alterations of the heart
rate, plasma epinephrine, PRA, or vasopressin. There
was also no relation between the change in mean blood
pressure and the baseline levels of the various neurohormonal variables.
The effect of alcohol on postural changes in blood
pressure was examined in 14 patients. As shown in
Table 5, the hypotensive effect of alcohol in the standing
position was comparable to that in the supine position,
and the heart rate response was also similar in both
positions.
Marked facial flushing developed in three subjects
after alcohol intake; such alcohol-induced flushing was
mild or absent in the remaining 13 subjects. The subjects with marked flushing showed greater alcoholinduced hypotension and tachycardia than those without flushing (Table 6). However, hypotension and
tachycardia were also evident in the nonflushing group.
Discussion
The present study showed that a single moderate
dose of alcohol lowered the blood pressure in hypertensive patients who were habitual drinkers. The alcohol
was taken with dinner, and the hypotensive effect was
evident in evening and night hours, but blood pressure
the next day was not influenced by the single dose of
alcohol. The average 20-hour ambulatory blood pressure value was also lower in the alcohol intake period
than in the control period. In our study, the order of
alcohol intake day and control day was randomized to
minimize the influences of various factors including the
order effect. Although food intake itself may induce
postprandial hypotension,29 the decrease in blood pressure after dinner was much greater in the alcohol intake
day than the control day despite similar changes in
blood glucose and serum insulin.
Earlier studies have provided inconsistent results
about the acute effects of alcohol on blood pressure,
with some studies showing an increase12"14 and others
showing a decrease15-17 or no change.19-20 Blood pressure was usually measured for short periods and only
occasionally for longer periods in these earlier studies.
Kawano et al
TABLE 4.
Depressor Effect of Alcohol
223
Hemodynamk Variables on the Alcohol Intake and Control Days in Eight Hypertensive Patients
Alcohol intake day
Control day
Variables
MBP (mm Hg)
HR (bpm)
CI (1/min/ra)
PVR (dyne • sec • cm"5)
LVFS(%)
LVESWS (103 dyne/cm2)
5 PM
7 PM
5 PM
7 PM
109±4
54±2
2.6+0.2
2,061+208
34±2
67 ±10
100±4
56±2
2.9±0J
1,791 ±225
37±2
56±7
106±5
52±3
2.6+0.2
2,096±268
35±1
62±5
89±3't
68±5't
3J±0J*t
1305±114*t
43±2't
37±5't
MBP, mean blood pressure; HR, heart rate; bpm, beats per minute; CI, cardiac index; PVR, peripheral
vascular resistance; LVFS, left ventricular fractional shortening; LVESWS, left ventricular end-systolic wall
stress.
"p<0.05 vs. the control day, tp<0.05 vs. 5 PM on the alcohol intake day.
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An increase in blood pressure has been observed within
30 minutes of the intake of alcohol in healthy young
men,12-14 and a significant reduction in blood pressure
occurred at 90 to 180 minutes after drinking in healthy
volunteers.1617 Howes and Reid21 reported a biphasic
response of blood pressure to acute alcohol loading at a
dose of 0.9 g/kg in healthy male subjects.21 Blood
pressure increased initially at 15 to 30 minutes, then
decreased at 4 to 8 hours after drinking. Stott et al22 also
observed a tendency for a reduction in blood pressure
up to 8 hours after the intake of 1.3 g/kg alcohol in
healthy volunteers. In their study, transient elevations in
blood pressure were seen in both the alcohol intake and
control periods. However, there have been few studies
on the acute effect of alcohol on blood pressure in
hypertensive patients. Potter et al13 reported that moderate drinkers but not mild drinkers with hypertension
showed an increase in blood pressure at 30 minutes
after the intake of 0.75 g/kg of ethanol.
These data taken together suggest that the increase in
blood pressure after a single dose of alcohol is transient
and terminates within 60 minutes, whereas the decrease
1-0.70, p4L01
to
ioo
no
no
-100
MBP b*for* drinking (mmHg)
§
-to
0
100
100
100
400
UO
Chang** In plaama HE (pg/M)
S
-to
a
S
I
tO
10
40
SO
(0
AQE(Yaara)
FIGURE 6.
Scatterplots show relation between changes in
mean blood pressure (MBP) induced by alcohol (difference
between 5 PM and 7 PM) and the MBP before drinking (upper
panel) or the age of the subjects (lower panel).
Chang** tn Heart Rat* (baats/Mn)
FIGURE 7. Scatterplots show relation between changes in
mean blood pressure (MBP) induced by alcohol and changes
in plasma norepinephrine (NE) (upper panel) or heart rate
(lower panel).
224
Hypertension
Vol 20, No 2 August 1992
TABLE 5. Changes in Supine and Standing Blood Pressure
and Heart Rate on the Alcohol Intake and Control Days in
Fourteen Hypertensive Patients
Control day
Alcohol intake day
Variables
Supine
Standing
Supine
Standing
AMBP (mm Hg)
AHR (bpm)
-3±2
2±1
-5±2
2±1
-16±3*
13±2'
-17±4«
14±3*
AMBP, change in mean blood pressure between 5 and 7 PM;
AHR, change in heart rate between 5 and 7 PM; bpra, beats per
minute.
*p<0.01 vs. the control day.
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in blood pressure induced by alcohol appears to begin
after 60 minutes and to last for several hours. In our
current study, only a decrease in blood pressure was
observed after alcohol intake. The acute pressor effect
of alcohol might have been masked because we analyzed
the blood pressure data as averages for each 2-hour
period from measurements made at 30-minute intervals. Intake of alcohol together with a meal may be
another reason for the lack of blood pressure elevation
in the present study, since the transient pressor effect of
ethanol may be due to gastric irritation or stress induced
by rapid ingestion of this substance in the laboratory
setting.11 It has been shown that the blood alcohol
concentration is maximal at 60-120 minutes after intake, and then falls gradually rwer the subsequent
several hours.12-17-22 Therefore, our present study and
earlier studies suggest that a single moderate dose of
alcohol mainly acts to lower blood pressure in humans.
The chronic effect of alcohol on blood pressure
appears to differ from its acute effect. Most epidemiological studies have demonstrated a positive relation
between the habitual level of alcohol intake and blood
pressure, with a high prevalence of hypertension being
found in regular drinkers.1-5 This positive relation has
been seen in white, black, and Asian populations. It has
also been shown that abstinence or restriction of alcohol
lowers blood pressure in hypertensive and normotensive
subjects.6-9 However, blood pressure measurement was
carried out in the daytime in these studies, despite the
fact that alcohol is usually consumed in the evening
hours. Thus, it is possible that the pressor effect of
chronic alcohol consumption has been overestimated in
earlier studies. Using ambulatory blood pressure monitoring, we have observed that repeated alcohol intake
lowers nighttime blood pressure and elevates early
morning blood pressure without changing the average
TABLE 6. Changes in Mean Blood Pressure and Heart Rate on
the Alcohol Intake and Control Days in Patients With Marked
Alcohol-Induced Flush and Those With Mild or No Flush
Control day
Variables
AMBP (mm Hg)
AHR (bpm)
Alcohol intake day
Flush ( - ) Flush ( + )
Flush ( - ) Flush ( + ) (» = 13)
(n=3)
-3±2
2±1
-3±3
2±1
-12±3*
10±2*
-26±7ft
25±5t4
AMBP, changes in mean blood pressure (MBP) between 5 and
7 PM; AHR, changes in heart rate (HR) between 5 and 7 PM; bpm,
beats per minute.
•p<U.01 vs. the control day.
1p<0.05 vs. the control day.
tp<0.05 vs. the patients without flush.
24-hour blood pressure in hypertensive patients.30
Therefore, the effect of alcohol on blood pressure may
be more complex than was realized.
A rise in blood pressure has been observed as one
manifestation of the withdrawal syndrome in alcoholic
patients.231 During alcohol withdrawal, there is excess
central nervous system excitability and adrenergic discharge, and plasma norepinephrine level peaks 12-24
hours after the cessation of alcohol intake.2-11 The
withdrawal hypothesis has been considered as a mechanism of the alcohol-related hypertension.2-32 In the
present study, blood pressure did not rise the day after
alcohol intake, suggesting that a single moderate dose of
alcohol may not be enough to cause a significant increase in blood pressure in relation to the withdrawal
phenomenon.
The hypotensive effect of alcohol was pronounced in
the patients who had a higher baseline blood pressure in
this study. It is difficult to determine the exact influence
of the basal blood pressure level, but it seems possible
that vascular responsiveness may be altered in patients
with advanced hypertension. In our preliminary study,
the hypotensive effect of alcohol on the ambulatory
blood pressure was also seen in normotensive subjects,
although it was not significant (unpublished data). Many
antihypertensive agents are effective in lowering blood
pressure in hypertensive humans and animals but have
little effect on normotensive humans and animals. The
effect of alcohol on blood pressure may also be influenced by age, since there was a negative correlation
between age and the alcohol-related change in blood
pressure. However, this relation was not confirmed to be
significant by stepwise regression analysis. The marked
reduction in nocturnal blood pressure produced by
alcohol ingestion in patients with advanced hypertension or elderly patients is potentially harmful, and
further long-term studies of this subject are required.
The fall in blood pressure after alcohol intake was
associated with an increase in heart rate and cardiac
output and with a decrease in peripheral vascular
resistance, indicating that the hypotensive effect of
alcohol is due to peripheral vasodilatation. It has been
shown that alcohol and its metabolites, acetaldehyde
and acetate, have a vasodilatory effect on isolated blood
vessels.1011 This action may be related to interference
with the movement or translocation, or both, of calcium
across the vascular smooth muscle cell membrane.10 The
increase in heart rate that we noted has been consistently observed in earlier studies. This tachycardia
appears to be due to sympathetic activation and contributes to the increase in cardiac output. Although
alcohol acts to depress myocardial function, this effect
can be masked by autonomic responses.20-33 The inCTease in cardiac output may prevent a further reduction in blood pressure since the hypotensive effect of
alcohol seems to be stronger in patients with heart
failure15 or autonomic failure.18
The significant depressor effect of alcohol observed in
this study could be related to the alcohol flush syndrome
that is common in Orientals. Alcohol flushing is caused
by the accumulation of acetaldehyde due to a genetic
deficiency of aldehyde dehydroxygenase. It has been
reported that Japanese subjects with an alcohol flush
show marked cardiac stimulation and peripheral vasodilation.34-35 In our current study, the hypotensive and
Kawano et al Depressor Effect of Alcohol
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tachycardic effects of alcohol were greater in the subjects with flushing than in those without it. Since the
subjects of the present study were Japanese and some of
them showed alcohol flushing, the characteristics of
subjects may explain the different blood pressure responses between this and earlier studies. Kupari et al34
have shown that the blood acetaldehyde level after
alcohol intake is high in subjects with alcohol flushing,
but it is too low to detect in those without flushing.
However, the hypotensive effect of alcohol may not be
produced by the accumulation of acetaldehyde alone,
since the subjects without flushing also showed a significant fall in blood pressure after drinking. Although
acetaldehyde has a vasodilatory action, the dilator effect
of alcohol appears to be greater than acetaldehyde, at
least in certain vascular beds.10
In the present study, plasma norepinephrine and
epinephrine levels increased while blood pressure decreased at 2 hours after alcohol intake. The increase in
plasma norepinephrine was marked in patients who
showed a large decrease in mean blood pressure. Thus,
the sympathetic nervous system appears to be activated
by the vasodilatory effects of alcohol and may then
prevent the worsening of hypotension. An alcoholinduced increase in plasma catecholamines has been
shown in many studies.12-17-21-22 The sympathetic nervous system may also contribute to the early transient
rise in blood pressure after alcohol intake, since Grassi
et al14 observed an increase in muscle sympathetic
nerve activity and blood pressure after alcohol ingestion
in normotensive subjects. The increase in plasma norepinephrine seems to reflect a change in the activity of
central and peripheral noradrenergic neurons,11-36 although reduced norepinephrine clearance might partly
be involved.21
It has been shown that alcohol influences autonomic
reflexes and blood pressure responses. Single or repeated doses of alcohol attenuate the pressor responses
to the cold pressor test, handgrip exercise, and intravenous methoxamine in healthy volunteers.37-38 Howes
and Reid21 have observed a relatively larger fall in the
erect blood pressure after drinking in normotensive
men, but standing and supine blood pressure fell similarly in our present study, suggesting that the influence
of a single dose of alcohol on orthostatic blood pressure
regulation is not significant.
As in other reports,17-22 PRA increased and vasopressin decreased after alcohol intake in our study. The
increase in PRA may reflect activation of the sympathetic nervous system and might prevent severe hypotension. The decrease in vasopressin does not appear to
play a role in alcohol-induced hypotension, since vasopressin has little effect on blood pressure at the plasma
levels observed.39 However, the suppression of vasopressin release probably contributed to the relatively
higher serum protein and hematocrit levels by stimulating diuresis.
Serum potassium levels decreased significantly after
alcohol intake, confirming the report by Puddey et al.17
This fall in serum potassium may be due to an intracellular shift induced by activation of the sympathoadrenal
axis.40 Insulin did not appear to play a role in this
hypokalemia since the changes in blood glucose and
serum insulin were similar between the alcohol and
control days. It is possible that such hypokalemia cou-
225
pled with sympathetic activation and cardiac changes
could participate in the development of alcohol-induced
arrhythmias.41
Finally, the present study indicated that the major
effect of acute alcohol consumption was to lower the
blood pressure in hypertensive subjects. This depressor
effect of alcohol was due to peripheral vasodilatation
and was accompanied by reflex tachycardia, an increase
in cardiac output, and activation of the sympathetic
nervous system. Since the alcohol-induced hypotensive
effect appeared to be more pronounced in individuals
with a higher basal blood pressure or in elderly patients,
it should be taken into account in the treatment of
hypertension. The ambulatory blood pressure monitoring may be useful for assessment of the blood pressure
in habitual drinkers. It is possible that the pressor effect
of alcohol has been overestimated, and the depressor
effect has been underestimated by measuring only the
daytime blood pressure.
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Hypertension. 1992;20:219-226
doi: 10.1161/01.HYP.20.2.219
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