Handgrip increases endothelin-1 secretion in normotensive young male offspring of hypertensive parents.

Abstract

We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents.
It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension.
Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery.
Group A had higher norepinephrine levels than group B throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p < 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p < 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square=7.59, p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not.
The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.

Full text

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1998;31;1362-1366
J. Am. Coll. Cardiol.
Dell'Italia, and PP Campa
E Mangieri, G Tanzilli, F Barilla, M Ciavolella, PE Puddu, C De Angelis, LJ

of hypertensive parents
Handgrip increases endothelin-1 secretion in normotensive young male offspring
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HYPERTENSION
Handgrip Increases Endothelin-1 Secretion in Normotensive Young
Male Offspring of Hypertensive Parents
ENRICO MANGIERI, MD, GAETANO TANZILLI, MD, FRANCESCO BARILLA`, MD,
MASSIMO CIAVOLELLA, MD, PHD, PAOLO E. PUDDU, MD, FACC, CLAUDIO DE ANGELIS, MD,
LOUIS J. DELL’ITALIA, MD,* PIETRO P. CAMPA, MD
Rome, Italy and Birmingham, Alabama
Objectives. We tested the hypothesis that an abnormal response
of plasma endothelin-1 (ET-1) is elicited by handgrip exercise
(HG) in young normotensive offspring of hypertensive parents.
Background. It has been hypothesized that ET-1 is involved in
blood pressure control and plays a pathophysiologic role in the
development of clinical hypertension.
Methods. Two groups of healthy male subjects, 11 with hyper-
tensive parents (group A) and 10 without a family history of
hypertension (group B), underwent 4 min of HG at 50% maximal
capacity. Heart rate and blood pressure and plasma levels of
ET-1, epinephrine and norepinephrine were measured at baseline,
peak HG, and after 2 (R2) and 10 (R10) min of recovery.
Results. Group A had higher norepinephrine levels than group
B throughout the test (baseline 181 ? 32 [SEM] vs. 96 ? 12 pg/ml,
p < 0.05; peak HG 467 ? 45 vs. 158 ? 12 pg/ml, p < 0.000001; R2
293 ? 46 vs. 134 ? 8 pg/ml, p < 0.01; R10 214 ? 27 vs. 129 ? 10
pg/ml, p < 0.0005); no significant difference in epinephrine levels
was detected. Compared with group B subjects, group A had
higher baseline ET-1 levels (1.07 ? 0.14 vs. 0.59 ? 0.11 pg/ml, p <
0.02), which increased to a greater extent at peak HG (1.88 ? 0.31
vs. 0.76 ? 0.09 pg/ml, p < 0.005) and R2 (2.46 ? 0.57 vs. 1.31 ?
0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16 ? 0.78
vs. 0.52 ? 0.09 pg/ml, p < 0.002). Multivariate analysis demon-
strated that only a family history of hypertension (chi-square ?
7.59, p ? 0.0059) and ET-1 changes during HG (chi-square ?
4.23, p ? 0.0398) were predictive of blood pressure response to
HG and that epinephrine and norepinephrine were not.
Conclusions. The response to HG in offspring of hypertensive
parents produced increased ET-1 plasma levels and resulted in a
sustained ET-1 release into the bloodstream during recovery
compared with offspring of normotensive parents. This may be an
important marker for future clinical hypertension.
(J Am Coll Cardiol 1998;31:1362–6)
©1998 by the American College of Cardiology
A body of evidence from experimental and clinical studies
suggests that endothelium plays an important role in the
control of vascular tone, in both normal physiology and disease
states (1,2). A complex interaction between endothelium-
derived vasodilating factors and endothelium-derived contract-
ing factors mediates the regulation of basal vascular tone and
modulates long-term structural responses of the smooth mus-
cle cells in the vascular wall (3). Among endothelium-derived
contracting factors, endothelin-1 (ET-1) is involved in arterial
pressure control by local actions (contraction of vascular
smooth muscle and activation of angiotensin-converting en-
zyme) and by systemic and central effects (resetting of baro-
ceptors, increase in sympathetic tone and modulation of
synaptic transmission) (4). Accordingly, it has been hypothe-
sized that ET-1 is involved in blood pressure elevation and
plays a pathophysiologic role in essential hypertension (1,2).
Previous studies have shown that postural changes and
acute volume expansion induce a transient but marked eleva-
tion of plasma ET-1 levels, suggesting that ET-1 acts as a stress
hormone (5,6). Recently, Noll et al. (7) reported that ET-1
levels are increased during mental stress only in normotensive
offspring of hypertensive parents. This finding indicates that
functional changes in endothelial regulation might be geneti-
cally determined and possibly contribute to the abnormal
circulatory response to mental stress in these subjects.
On the basis of genetic factors and environmental compo-
nents, first-degree relatives of essential hypertensive patients
are known to be at risk of developing hypertension (8). In
addition, specific neurohumoral and hemodynamic hyperreac-
tivity to various stresses, such as isometric handgrip exercise
(HG), has been recognized in normotensive offspring of hy-
pertensive parents, and thus linked to the hereditability of
hypertension (7,9). In healthy humans, HG causes: 1) a rapid
heart rate increase in the initial seconds of exercise, and a
subsequent slow further increase during the work period; and
2) a rise in arterial blood pressure, which increases slightly
throughout the contraction period. Both heart rate and blood
pressure return to basal levels soon after the end of the
From the Second Division of Cardiology, Institute of Cardiac Surgery,
University “La Sapienza,” Rome, Italy; and *Division of Cardiovascular Dis-
eases, University of Alabama at Birmingham, Birmingham, Alabama. This study
was supported by Grant 5/15/02/003 from the Ministero Universita ` e Ricerca
Scientifica e Tecnologica-Italia, Rome.
Manuscript received August 25, 1997; revised manuscript received January
16, 1998, accepted January 26, 1998.
Address for correspondence: Dr. Enrico Mangieri, Via Parenzo, 1, 00198
Rome, Italy.
JACC Vol. 31, No. 6
May 1998:1362–6
1362
©1998 by the American College of Cardiology
Published by Elsevier Science Inc.
0735-1097/98/$19.00
PII S0735-1097(98)00087-4
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voluntary contraction. Such circulatory response has been
explained by the combined action of vagal withdrawal and
sympathoadrenomedullar activation (10,11). We hypothesized
that in normotensive offspring of hypertensive parents isomet-
ric HG would cause ET-1 release in the bloodstream that
would differ from young healthy subjects without a family
history of hypertension.
Methods
Patients. Twenty-one young men were enrolled in this
study. All were normotensive and free of cardiovascular dis-
eases, as evidenced by clinical examination and laboratory
findings. Smokers and physically trained and overweight indi-
viduals (weight ?10% than ideal) were excluded. Group A
included 11 healthy sons (mean age 25.4 ? 1.5 years) of
patients followed-up at our Institution because of medically
treated essential hypertension. All group A subjects underwent
24-h blood pressure monitoring. Only those with a normal
profile were entered into the protocol. Group B included 10
healthy men (mean age 27.3 ? 0.5 years), who were sons of
normotensive outpatients. The study protocol was approved by
the local Medical Ethics Committee, and informed consent
was obtained from each subject.
Study protocol. The young men were studied in a labora-
tory (room temperature 22° to 24°C) during the morning hours
(9 to 12 AM) after an overnight fast. They were in the supine
position for at least 1 h before the start of HG exercise and
were instructed to avoid Valsalva-like maneuvers. HG was
performed with a calibrated handgrip dynamometer (Vigorim-
eter Martin, Germany). The men performed the maximal
compressive force with the dominant arm three times, at 3 min
intervals. After 30 min rest, 50% of the average maximal
voluntary contraction was performed for 4 min by each subject.
Heart rate and arterial blood pressure were obtained by
electrocardiogram and cuff sphygmomanometer at baseline, at
peak exercise (peak HG), and every 2 min (R2) throughout an
average recovery period of 10 min (R10).
A short 18-gauge polyethylene cannula was inserted into an
antecubital vein of the nondominant arm 30 min before the
beginning of the study, and kept patent by slow infusion of 5%
dextrose. Blood samples for ET-1 and catecholamine levels
were drawn immediately before the beginning of the test
(basal), at peak HG, and after R2 and R10.
Biochemical assays. Blood samples were collected into
prechilled tubes (Becton Dickinson Vacutainer Systems) con-
taining EDTA-K3 (15%) and aprotinin (1,000 KIU/ml of
blood) and promptly centrifuged at 1,600g for 15 min at 4°C.
Plasma was pipetted into polypropylene tubes and stored at
?80°C until assayed. At the time of analysis, plasma samples
were acidified with an equal volume of 0.1% trifluoroacetic
acid and centrifuged at 2,500g at 4°C for 30 min to remove
proteolytic activity. Plasma compounds tested were first con-
centrated by extraction through C18 Sep-PaK cartridges (Mil-
lipore Corporation).
For catecholamine assay, 2 ml of plasma were mixed with 8
ml of a 0.1 mol/liter phosphate buffer (pH 7.0) and 20 ?l of
internal standard solution (224 ng/ml DHBA) and applied to a
small polypropylene column filled with 2 ml of preswollen
ion-exchanger Sephadex CM. Before use, the packed column
was washed with 10 ml of 0.1 mol/liter phosphate (pH 7.0).
After the samples had been tested, the column was rinsed with
10 ml of distilled water and 4 ml of 0.1 perchloric acid.
Catecholamines were eluted with 3 ml of 0.5 mol/liter perchlo-
ric acid, and the eluate was collected in 15-ml conical tubes.
Two milliliters of Tris buffer (1.5 mol/liter, pH 9.3), containing
0.06 mol/liter EDTA and 20 mg of activated alumina, were
added. The tube was vortex mixed for 2 min. The supernatant
was removed by aspiration, and the alumina was washed twice
with 2 ml of water, centrifuging between each wash (3000g,
3 min). After the second washing, as much water as possible
was removed by aspiration and by drying the wall tube with
little strips of filter paper. Catecholamines were eluted from
the alumina with 100 (1 of 0.1 mol/liter acetic acid after vortex
mixing for 2 min. After centrifugation, the supernatant was
removed, and 25 ?l were injected into the high performance
liquid chromatographic system (12).
For ET-1 assay, Sep-Pak columns were first activated with
0.1% trifluoroacetic acid buffer, loaded with 2 ml plasma and
then washed with 0.1% trifluoroacetic acid buffer. The retained
material was eluted with 3 ml of a buffer containing acetonitril
(60%) in 0.1% trifluoroacetic acid and dried under vacuum by
a centrifugal evaporator system (Gyrovap, Howe and Co.,
London, UK). The radioimmunoassay of the reconstituted
pellet was performed by a commercial ET-1 radioimmunoassay
kit (Peninsula Laboratories). Each measurement was per-
formed twice, and the average value of the two measurements
was generally considered, although differences between the
two measurements were ?5%. In two cases that had one of the
baseline measurements far above normal ranges, only the
other measurement was taken into account. Cross-reactivity of
the system for ET-1 was 100%; it was lower than 7% for both
endothelin-2 and endothelin-3, according to the supplier.
Intraassay and interassay variations in our laboratory were
?10%. Recovery was 80%. Plasma ET-1 levels are expressed
as picograms per milliliter.
Statistical analysis. All data are expressed as mean value ?
1 SEM. Statistical analysis was performed with BMDP statis-
tical software (13). Analysis of variance and t tests were
performed with the Bonferroni correction (BMDP-7D). Be-
cause data represent time (protocol)-related repetitions, a
repeated measures model with structured covariance matrices
(BMDP-5V: type ? compound symmetry) was used as a means
of comparing multivariately the studied groups (14). Models
Abbreviations and Acronyms
ET-1 ? endothelin-1
HG
? handgrip exercise
R
? recovery phase
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were set to explain the dependent variable mean blood pres-
sure reading (from baseline to peak HG, R2 and R10) based
on both time-constant (age, weight and height) and time-
varying (respectively from baseline to peak HG, R2 and R10:
heart rate, ET-1, epinephrine and norepinephrine) covariates
(13,14). The analysis consists of a multivariate analysis of
variance model used to assess the power of the single covari-
ates (norepinephrine, epinephrine and ET-1) in determining
the event (changes in mean arterial pressure during all steps of
the HG test). To construct the dependent variable, the formula
diastolic blood pressure ? (systolic blood pressure ? diastolic
blood pressure)/3 was used. The Akaike information criterion
was used to select the most successful model (13). As a means
of approaching possible cause and effect relations between
time-varying variables (xi independent variables) and mean
blood pressure (y dependent variable), linear regression
(BMDP-1R) was used, and several models were compared,
entering different delta values from baseline to peak HG, R2
and R10 periods, respectively, for both xi and y variables.
Mean squared residuals and r2values were used to test
significance. A p value ? 0.05 was considered significant.
Results
The average values of the evaluated variables are presented
in Table 1.
Healthy offspring of hypertensive parents (group A). Start-
ing from an average value of 64 ? 7 beats/min at baseline,
heart rate increased to 96 ? 4 beats/min at peak HG (p ?
0.002) and decreased to 76 ? 4 beats/min (p ? NS) and 70 ?
3 beats/min (p ? NS) at R2 and R10, respectively. Systolic
blood pressure increased from 120 ? 3 mm Hg to 163 ?
4 mm Hg (p ? 0.00001) at peak HG, returned to basal values
at R2 and persisted unchanged until R10 (131 ? 3 mm Hg, p ?
NS and 122 ? 3 mm Hg, p ? NS, respectively). A similar trend
was observed for diastolic blood pressure, with an increase
from 77 ? 2 mm Hg to 106 ? 3 mm Hg (p ? 0.000005) and a
persistent decrease to basal values at R2 and R10 (82 ?
2 mm Hg, p ? NS and 78 ? 2 mm Hg, p ? NS, respectively).
The average basal ET-1 levels (1.07 ? 0.14 pg/ml) were
within the normal ranges reported in the literature (7) and
showed a progressive and significant increase from 1.88 ? 0.31
pg/ml (p ? 0.02) at peak HG to 2.46 ? 0.66 pg/ml (p ? 0.02)
at R2 and to 3.16 ? 0.78 pg/ml (p ? 0.02) at R10. Norepi-
nephrine values showed a significant increase at peak HG
compared with baseline (181 ? 31 pg/ml vs. 466 ? 45 pg/ml,
p ? 0.001), with a decrease to 293 ? 45 pg/ml (p ? NS) and
214 ? 26.55 pg/ml (p ? NS) at R2 and R10, respectively.
Epinephrine also changed from 35.73 ? 5.06 pg/ml to 68.89 ?
12.94 pg/ml (p ? 0.05) at peak HG, whereas R2 and R10 values
showed no significant differences in comparison with basal
values (49.01 ? 14.91 pg/ml, p ? NS, and 33.15 ? 4.10 pg/ml,
p ? NS).
Healthy offspring without family history of hypertension
(group B). Starting from an average value of 71 ? 1 beats/min
at baseline, heart rate increased to 83 ? 3 beats/min at peak
HG (p ? 0.01) and decreased to 68 ? 1 beats/min (p ? NS)
and 66 ? 1 beats/min (p ? 0.05) at R2 and R10, respectively.
Systolic blood pressure increased from 121 ? 2 mm Hg to
157 ? 5 mm Hg (p ? 0.0001) at peak HG and returned to basal
values at R2 and R10 (121 ? 2 mm Hg, p ? NS and 115 ?
2 mm Hg, p ? 0.05, respectively). A similar trend was observed
for diastolic blood pressure, with an increase from 77 ?
1 mm Hg to 103 ? 5 mm Hg (p ? 0.00001) and a persistent
decrease to basal values at R2 and R10 (79 ? 2 mm Hg, p ?
NS and 76 ? 2 mm Hg, p ? NS, respectively).
The average basal ET-1 level (0.59 ? 0.11 pg/ml) rose
progressively to 0.76 ? 0.09 pg/ml (p ? 0.05) at peak HG and
to 1.31 ? 0.23 pg/ml (p ? 0.02) at R2 and decreased to 0.52 ?
0.08 pg/ml (p ? NS) at R10. Norepinephrine and epinephrine
plasma levels showed a significant increase at peak HG com-
pared with baseline, from 95 ? 11 pg/ml to 158 ? 11 pg/ml
(p ? 0.000001) and from 28.16 ? 6.50 pg/ml to 50.13 ? 8.06
pg/ml (p ? 0.02), respectively. During recovery there was a
progressive reduction, although average values remained
slightly higher than baseline for norepinephrine (134 ? 8
pg/ml, p ? 0.001 and 129 ? 10 pg/ml, p ? 0.05) and
Table 1. Average Values of Evaluated Variables in Groups A and B
SBP
(mm Hg)
DBP
(mm Hg)
MAP
(mm Hg)
HR
(beats/min)
ET-1
(pg/ml)
EPI
(pg/ml)
NEPI
(pg/ml)
Group A
Basal
Peak HG
R2
R10
Group B
Basal
Peak HG
R2
R10
120 ? 4
163 ? 4‡
131 ? 3
122 ? 3
77 ? 2
106 ? 3‡
82 ? 2
78 ? 2
91 ? 7
125 ? 9‡
99 ? 7
93 ? 8
64 ? 7
96 ? 4‡
76 ? 4
71 ? 3
1.07 ? 0.14
1.88 ? 0.31†
2.46 ? 0.57†
3.16 ? 0.78†
35.73 ? 5.06
68.89 ? 12.94*
49.01 ? 14.91
33.15 ? 4.10
181 ? 31
466 ? 45‡
293 ? 46
214 ? 27
121 ? 3
157 ? 5‡
122 ? 2
115 ? 2*
77 ? 1
103 ? 4‡
79 ? 2
76 ? 2
91 ? 4
121 ? 14‡
93 ? 6
89 ? 4
71 ? 1
83 ? 3†
68 ? 1
66 ? 1*
0.59 ? 0.11
0.76 ? 0.09*
1.31 ? 0.23*
0.52 ? 0.09
28.16 ? 6.50
50.13 ? 8.06*
36.29 ? 4.06*
28.80 ? 5.41
95 ? 11
158 ? 12‡
134 ? 8‡
129 ? 10*
*p ? 0.05, †p ? 0.02 and ‡p ? 0.001 versus basal values. Data presented are mean value ? SD. DBP ? diastolic blood
pressure; EPI ? epinephrine; ET-1 ? endothelin-1; HG ? handgrip; HR ? heart rate; MAP ? mean arterial blood
pressure; NEPI ? norepinephrine; R2 ? 2 min of recovery; R10 ? 10 min of recovery; SBP ? systolic blood pressure.
1364
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HANDGRIP-INDUCED ET-1 ABNORMAL ACTIVATION
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May 1998:1362–6
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epinephrine values did not differ from baseline (36.29 ? 4.06
pg/ml, p ? 0.05, and 28.8 ? 5.41 pg/ml, p ? NS).
Univariate comparisons between groups. Systolic and dia-
stolic blood pressure levels, as well as heart rate, did not differ
significantly between groups during all evaluated times.
Baseline ET-1 plasma levels, although always within normal
ranges, were higher in group A than in group B (p ? 0.02). At
peak HG, the ET-1 response increased in group B only,
although average values remained higher in group A (p ?
0.005). At R2, a significantly higher increase in group A was
found (p ? 0.05), whereas at R10 a statistically significant (p ?
0.002) opposite behavior was evident, toward a further in-
crease in group A and a decrease to basal values in group B
(Fig. 1).
Norepinephrine levels were significantly higher at baseline
(p ? 0.05) and there was a greater increase at peak HG (p ?
0.001) in group A than in group B. A similar behavior between
the groups was found at R2 and R10; however, average plasma
levels were significantly higher in group A at both times (p ?
0.01 and p ? 0.001, respectively). Average epinephrine values
did not differ significantly between groups during all evaluated
times.
Multivariate comparisons between groups. The highest
Akaike information criterion (?274.82) was found in the
model where mean blood pressure response to HG (dependent
variable) did not include age among the explanatory covari-
ates. Age did not contribute significantly enough (chi-square ?
0.62, p ? NS) to explain the dependent variable mean blood
pressure in the models in which it was considered. None of the
remaining time-constant covariates were contributory (weight:
chi-square ? 0.29, p ? NS; height: chi-square ? 0.68, p ? NS).
Among time-varying covariates, neither epinephrine (chi-
square ? 0.69, p ? NS) nor norepinephrine (chi-square ?
1.43, p ? NS) contributed significantly to explain the depen-
dent variable, and heart rate did so with only borderline
significance (chi-square ? 3.27, p ? 0.0704). By contrast, ET-1
was a significant time-varying covariate (chi-square ? 4.23, p ?
0.0398), as was the grouping covariate (presence vs. absence of
family history of hypertension: chi-square ? 7.59, p ? 0.0059).
Interestingly, the dependent variable was explained by time
(chi-square ? 196.13, p ? 0.00005) but not by the interaction
term grouping*time (chi-square ? 1.58, p ? 0.66). Of the
several linear regression models tested in an attempt to explain
the delta changes (from baseline) of mean blood pressure at
different time points of the protocol, none was statistically
significant.
Discussion
The present findings confirm earlier observations of 1)
higher basal levels of norepinephrine, 2) a more pronounced
responsiveness of blood pressure and heart rate during HG,
and 3) an exaggerated response to sympathoadrenal stimula-
tion by HG in persons with a family history of hypertension.
The novel finding of the current investigation is the response of
plasma ET-1 levels during HG exercise in young normotensive
subjects with family history of hypertension. We found that
ET-1 plasma levels were higher throughout the four assessed
steps of the HG test and that the ET-1 release into the
bloodstream was found to progressively increase throughout
recovery. The results of the multivariate analysis demonstrated
that the change in plasma ET-1 levels during HG exercise and
recovery was the only variable that differed between offspring
of hypertensive versus normotensive parents.
Physiologic and pathophysiologic effects of ET-1. ET-1,
the most important endothelin known so far, is produced in the
endothelium and by smooth muscle cells (9,15). In addition to
powerful vasoconstricting properties that exceed those of other
cardiovascular hormones, ET-1 potentiates at very low concen-
trations the contraction induced by norepinephrine and sero-
tonin in human arteries (16). It may also induce hypertrophy of
smooth muscle cells and is mitogenic to various cell lines,
including vascular smooth muscle cells (17). ET-1 could con-
tribute to blood pressure increases if production of this peptide
was increased (18,19). However, only in rare cases has a
pathogenetic role of ET-1 in raising blood pressure been
reported (20). Different reports have shown plasma ET-1 to be
slightly increased or normal in hypertensive humans (21–24).
As ET-1 acts mainly as a paracrine agent, rather than as a
circulating hormone, ET-1 secretion is mostly abluminal, to-
ward the vascular wall, and circulating levels are the result of
spillover into the blood stream (25). Thus, it is not surprising
that ET-1 plasma levels are similar in normotensive and
hypertensive individuals.
Noll et al. (7) reported for the first time an increase in
plasma endothelin levels during mental stress only in offspring
of hypertensive parents. They measured sympathetic nerve
activity and plasma levels of norepinephrine and endothelin
under resting conditions, during hypoxia, and during a mental
stress test in 10 normotensive offspring of hypertensive parents
and in 8 offspring of normotensive parents. During hypoxia,
norepinephrine and endothelin levels increased to the same
extent in both groups, whereas mental stress induced an
increase of norepinephrine and endothelin plasma levels and
of blood pressure only in offspring of hypertensive parents.
Their results support the concept that an early paracrine
Figure 1. Endothelin-1 levels throughout handgrip isometric exercise
test in the two groups with (Group A) and without (Group B) family
history of hypertension.
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JACC Vol. 31, No. 6
May 1998:1362–6
MANGIERI ET AL.
HANDGRIP-INDUCED ET-1 ABNORMAL ACTIVATION
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