N Ito, A Takeshita, S Higuchi and M Nakamura

Venous abnormality in normotensive young men with a family history of hypertension.

Print ISSN: 0194-911X. Online ISSN: 1524-4563
Copyright 1986 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Hypertension
doi: 10.1161/01.HYP.8.2.142
1986;8:142-146 Hypertension.
http://hyper.ahajournals.org/content/8/2/142
World Wide Web at:
The online version of this article, along with updated information and services, is located on the

http://hyper.ahajournals.org//subscriptions/
is online at: Hypertension Information about subscribing to Subscriptions:

http://www.lww.com/reprints
Information about reprints can be found online at: Reprints:

document. Permissions and Rights Question and Answer process is available in the
Request Permissions in the middle column of the Web page under Services. Further information about this
Office. Once the online version of the published article for which permission is being requested is located, click
can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Hypertension
Requests for permissions to reproduce figures, tables, or portions of articles originally published in Permissions:
by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from
by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from
VEINS IN MEN WITH HYPERTENSIVE RELATIVES//^ et al. 143
Subjects and Methods
Of approximately 2,000 students at the University
of Kyushu who had blood pressure measured, 35 nor-
motensive students volunteered for the study. Normal
blood pressure was defined as systolic and diastolic
pressure less than 140 and 90 mm Hg, respectively.
The subjects were all healthy men with no significant
medical history. Seventeen subjects (mean age, 22
0.8 [SE] years) had a family history of essential hyper-
tension in first-degree relatives, whereas 18 other sub-
jects (mean age, 22 0.7 years) had no such family
history. It was difficult to determine the presence or
absence of a family history of hypertension since the
relatives of most students lived at a distance. However,
the blood pressures of the subjects' parents were
recorded locally and results were forwarded to our
laboratory. Only subjects who had documented hyper-
tension or normal blood pressure recordings in first-
degree relatives were included in this study. The study
protocol was explained and informed consent was ob-
tained from all subjects.
Venous distensibility was determined by obtaining
venous pressure-volume curves. "
12
A single-chamber
water-filled plethysmograph was used for recording
volume changes in a segment of the left forearm. Sub-
jects wore light clothing and felt comfortably warm at
a room temperature of 18 to 22 C.
The left forearm was enclosed in an acrylic plastic
plethysmograph. Warm water (temperature, 32-34C)
was added to 26 cm above the upper aspect of the
forearm. The external water pressure initially col-
lapsed the veins under these conditions, but the arterial
inflow caused the venous pressure to reach a level
slightly higher than that of the external water pressure.
The difference between the pressure within the veins
and the external water pressure surrounding them is the
distending, or transmural, pressure. Venous pressure
was measured through a polyethylene tube inserted
into a superficial vein in the segment of the forearm
enclosed in the plethysmograph. Transmural venous
pressure was measured by placing the reference level
of the pressure transducer at the surface level of the
water in the plethysmograph. Transmural venous pres-
sure in subjects at rest under these conditions is less
than 1.5 mm Hg. The blood volume in the forearm
vessels at this low transmural venous pressure is ap-
proximately 1.3 ml/100 ml of forearm volume. Under
resting conditions, transmural venous pressure and
volume are constant and reproducible in a given sub-
ject and are similar between subjects.
13
Changes in the forearm blood volume were recorded
during stepwise increases in transmural venous pres-
sure to 30 mm Hg by inflating a cuff on the arm
proximal to the plethysmograph (Figure 1). Trans-
mural venous pressure was increased slowly to mini-
mize nonuniform filling of the veins
14
and was held
constant at each step until changes in forearm blood
volume stabilized (see Figure 1). Changes in the ve-
nous volume were reflected by the changes in forearm
blood volume, which were measured by recording
changes in the height of water. Increases in volume in
response to congestion of the forearm occur primarily
in vessels in which resting pressure is less than 10 mm
Hg.
13
Venous pressure-volume curves were construct-
ed by plotting changes of forearm blood volume
(ml/100 ml of forearm volume) against corresponding
levels of transmural venous pressure.
To investigate the contribution of a-adrenergic
mechanisms to venous distensibility, measurements of
venous distensibility were obtained before and after
intravenous administration of phentolamine at a rate of
1 mg/min for 5 minutes. It has been previously shown
in normotensive subjects and in subjects with border-
line hypertension that this dose of phentolamine is
sufficient to block the reflex venoconstriction in re-
sponse to deep inspiration when the occluded-vein
technique is used.
9
The data are expressed as means SE. Compari-
sons of the venous pressure-volume curves between
the two groups or before and after phentolamine ad-
ministration in the same group were done using two-
way analysis of variance for unequal cell size.
15
'
16
In
addition, we compared the changes in forearm blood
volume at each level of transmural venous pressure
between the two groups, using unpaired Student's t
test, and before and after phentolamine administration
in the same group, using paired t test. A p value less
than or equal to 0.05 was considered statistically sig-
nificant.
Results
Systolic blood pressure at the time of study was
significantly higher in subjects with a family history of
essential hypertension (127 2 mm Hg) than in sub-
jects with no family history of hypertension (118 2
mm Hg;p < 0.05). Diastolic pressure was not differ-
ent between the two groups (64 2 mm Hg and 63
2 mm Hg, respectively). Resting forearm venous pres-
sure was not different between subjects with a family
history of hypertension (2.7 0.4 mm Hg) and those
with no family history of hypertension (2.5 0.6 mm
Hg). In addition, the forearm blood volume enclosed
in the plethysmograph was not different between the
two groups (569 21 ml for subjects with a family
history of hypertension and 545 19 ml for subjects
with no family history).
A FOREARM
VENOUS
VOLUME
60 uc
FIGURE 1. Recordings of the changes in venous volume in the
forearm during stepwise increases in transmural venous pres-
sure from the baseline level to 30 mm Hg.
by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from
144 HYPERTENSION VOL 8, No 2, FEBRUARY, 1986
TABLE 1. Changes in Forearm Blood Volume at Graded Transmural Venous Pressure Before and After Phentolamine
Family history of hypertension
Present (n = 17)
Before phentolamine
After phentolamine
Absent (n = 18)
Before phentolamine
After phentolamine
5
1.30.1
1.30.1*
1.60.1
1.7 + 0.1
Transmural
10
2.1 0.1
2.20.1
2.40.1
2.50.1
venous pressure
15
2.6 + 0.1
2.70.1
2.90.1
3.00.1
(mm Hg)
20
3.00.1
3.00.l
3.3O.l
3.3 + 0.2
30
3.5+0.1*
3.5+0.1
3.90.1
3.90.2
Values are means + SE. Changes in forearm blood volume measured as ml/100 ml of forearm volume. The venous
pressure-volume relationship was compared as the curve between the two groups of subjects.
*p < 0.05, between-group comparison at the same level of transmural venous pressure.
The venous pressure-volume relationship at trans-
mural venous pressure of 5, 10, 15, 20, and 30 mm Hg
in the two groups is shown in Table 1 and Figure 2.
Before phentolamine administration, the venous pres-
sure-volume curve in subjects with a family history of
hypertension was shifted toward the pressure axis as
compared to that in subjects with no family history of
hypertension (p < 0.001; see Figure 2). The increase
in venous volume before phentolamine administration
was less (p < 0.05) at a transmural venous pressure of
30 mm Hg and tended to be less (p < 0.1) at trans-
mural venous pressures of 5 and 20 mm Hg in subjects
with hypertensive relatives as compared with that in
subjects with no hypertensive relatives.
Phentolamine did not alter the venous pressure-vol-
ume relationship in either group (see Table 1). After
phentolamine administration, the venous pressure-vol-
ume relationship in subjects with a family history of
hypertension was still shifted toward the pressure axis
(p < 0.001) as compared to that in subjects with no
family history of hypertension. The increase in venous
volume after phentolamine administration was less (p
< 0.05) at the transmural venous pressure of 5 mm Hg
and tended to be less (p < 0.1) at transmural venous
pressures of 10, 20, and 30 mm Hg in subjects with
hypertensive relatives as compared with that in sub-
jects with no hypertensive relatives.
Discussion
The method employed in this study has been widely
used to study venous distensibility and constriction in
humans,
9
'"-
|3> l7
~
19
and the validity of this method has
been extensively studied and discussed." However, a
discussion of several points is relevant here.
First, comparisons of changes in venous volume at
various levels of transmural venous pressure between
the two groups are valid only when the reference point
or the baseline of venous volume and transmural ve-
nous pressure is similar between the two groups. The
relationship between the changes in venous volume
and transmural venous pressures is curvilinear (see
Figure 2). Therefore, if the baseline venous volume
were greater in subjects with a family history of hyper-
tension, the increases in venous volume would be less
as transmural venous pressure was increased. In this
regard, however, use of a water-filled plethysmograph
has an important advantage over a strain gauge ple-
thysmograph, since the external water pressure of 20
mm Hg reduces the transmural venous pressure to vir-
tually zero and produces a large decrease in venous
volume to the baseline volume.
13
In previous studies, we have shown that venous
volume was reduced to the minimal baseline volume
when the external water pressure was above 12 mm
Hg.
9
- " It also has been shown that the minimal base-
line volumes under the external water pressure of 20
mm Hg are similar between subjects and are reproduc-
ible in a given subject.
13
In the present study, baseline
transmural venous pressure was less than 1.5 mm Hg
and was not different between the two groups. Thus, it
appears reasonable to assume that the changes in ve-
nous volume at various levels of transmural venous
pressure were examined from a comparable reference
point in the two groups.
I
E 5
8
_ 2
.
I"
t> 20
Transmural Vonout Prtsujr*
(mmHQ)
FIGURE 2. Venous pressure-volume curves before phentola-
mine administration in subjects with a family history of hyper-
tension (A) and in subjects with no family history of hyperten-
sion (). The venous pressure-volume curve in subjects with a
family history of hypertension was shifted downward toward the
pressure axis (p < 0.001) as compared to the curve in subjects
with no family history of hypertension.
by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from
VEINS IN MEN WITH HYPERTENSIVE RELATIVES//^ et al. 145
Second, transmural venous pressure was measured
in a large vein in the forearm segment under the water
column. Measured transmural venous pressure may
not be representative of the pressure at other segments
of the forearm veins if venous filling is not even be-
tween various segments of the veins. However, a pre-
vious study has suggested that uniform pressure in-
creases can be achieved by slowly increasing venous or
cuff pressure.
14
In our study, transmural venous pres-
sure was held constant at each step until changes in the
forearm venous volume stabilized (see Figure 1).
The possible difference in transmural venous pres-
sure between small and large veins also should be
considered. Resting venous pressure in small veins
may be higher than that in large veins; however, trans-
mural venous pressure under external water pressure
should be similar between small and large veins if
small as well as large veins have been collapsed by
external water pressure. The results of previous studies
have suggested that small and large veins are collapsed
under the external water pressure above 10 to 12 mm
Hg.
517
Third, the temperature of water was held at 32 to
34C in this study. It has been suggested that forearm
veins are relaxed under these conditions
18
and there
is minimal a-adrenergic venoconstriction in normal
subjects.
1219
Thus, this study examined the venous
pressure-volume relationship of forearm veins that
were relaxed and had minimal a-adrenergic venocon-
striction.
The results of this study indicate that the pressure-
volume relationship of the forearm veins is shifted
toward the pressure axis in normotensive young sub-
jects with a family history of hypertension as compared
with that in subjects with no family history of hyper-
tension. These findings suggest that distensibility of
the forearm veins in the relaxed state is reduced in
normotensive subjects with a family history of hyper-
tension.
Recently, Sallerfors et al.
10
examined forearm ve-
nous volume at the occluding cuff pressure of 20 mm
Hg in normotensive subjects with or without a family
history of hypertension. Venous volume was measured
using a strain gauge plethysmograph in the forearm
held at the level of the heart. Under such conditions,
resting venous volume may differ between groups;
therefore, the possibility that changes in venous vol-
ume may have been examined from a different refer-
ence point cannot be excluded. In addition, their sub-
jects were middle-aged. Thus, factors other than a
family history of hypertension may have contributed to
venous changes. Nevertheless, forearm venous vol-
ume at the occluding cuff pressure of 20 mm Hg was
less in normotensive subjects with a family history of
hypertension than in subjects with no family history of
hypertension,
10
which is in concord with the results
of the present study.
Although the mechanisms of venous abnormality
found in subjects with a family history of hypertension
cannot be determined from these studies, several pos-
sibilities should be considered. Venous changes in
subjects with a family history of hypertension may
have resulted from nonspecific mechanisms such as
increased venous pressure or salt intake. However,
resting venous pressure measured in a forearm vein
was not different between the two groups. Venous
changes in subjects with a family history of hyperten-
sion may have been caused by a higher salt intake,
since the level of salt intake may affect venous disten-
sibility.
17
Because this study was done in nonhospital-
ized subjects, we were not able to control or assess the
level of average daily salt intake. Daily salt intake
varies widely in an individual subject
20
; however, high
salt intake has been shown to alter venous distensibility
only in susceptible subjects.
17
Thus, even if salt intake
were different between the two groups, the difference
in salt intake by itself should not account for the differ-
ence in venous distensibility between the two groups.
If venous abnormality in subjects with a family history
of hypertension is related to salt intake, salt suscepti-
bility, which may be a hereditary abnormality in these
subjects,
2
would be an important contributing factor.
Venous changes in subjects with a family history of
hypertension might also be related to augmented a-
adrenergic venoconstriction, since previous studies
have suggested that a-adrenergic vasoconstriction may
be exaggerated in these subjects' and that venous
changes in patients with borderline hypertension are
due in part to augmented a-adrenergic venoconstric-
tion.
9
To examine this possibility, we studied the ve-
nous pressure-volume relationship before and after the
administration of phentolamine, 5 mg i.v. given in 5
minutes. Phentolamine did not alter the venous pres-
sure-volume relationship in either group.
In interpreting these results several questions should
be addressed. First, we should consider the possibility
that the dose of phentolamine might have been insuffi-
cient to block a-adrenergic effects on veins. However,
it has been previously shown that this dose of phentola-
mine blocks reflex venoconstriction caused by deep
breathing in both normal subjects and patients with
borderline hypertension.
9
a-Adrenergic blockade by
phentolamine is much more effective in veins than in
arteries.
19
Second, we should consider the possibility
that increased arterial blood flow after phentolamine
administration influenced the venous pressure-volume
curve. It has been shown, however, that changes in
arterial blood flow alter the rates of increase in venous
volume but do not alter the venous pressure-volume
relationship.
l2
-
18
Third, we might consider the possible
role of /3-adrenergic mechanisms in venous changes in
subjects with a family history of hypertension. Howev-
er, a previous study indicated that /3-adrenergic stimu-
lation with isoproterenol administered into the brachial
artery to avoid systemic effects did not constrict or
dilate forearm veins in humans.
12
Thus, our findings suggest that venous changes ob-
served after phentolamine administration in subjects
with a family history of hypertension did not result
from exaggerated a-adrenergic mechanisms. Howev-
er, it should be noted that the venous pressure-volume
relationship was examined while the veins were re-
by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from
by guest on April 25, 2014 http://hyper.ahajournals.org/ Downloaded from