1. No category

Effects of clonidine on 24-hour hormonal secretory patterns, cardiovascular hemodynamics,
and central nervous function in hypertensive adolescents.
R M Boyar, D F Fixler, N M Kaplan, R M Graham, K P Price, J J Chipman and W P Laird
Hypertension. 1980;2:83-89
doi: 10.1161/01.HYP.2.1.83
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1980 American Heart Association, Inc. All rights reserved.
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Effects of Clonidine on 24-Hour Hormonal Secretory
Patterns, Cardiovascular Hemodynamics, and Central
Nervous Function in Hypertensive Adolescents
ROBERT M. BOYAR, M.D.,
DAVID F. FIXLER, M.D.,
ROBERT M. GRAHAM, M.D.,
JOHN J. CHIPMAN, M.D.,
N O R M A N M. KAPLAN,
KENNETH P. PRICE,
AND W. PENNOCK LAIRD,
M.D.,
M.D.,
M.D.
SUMMARY To assess the potential of antihypertensive drugs for interference with somatic growth and sexual development in hypertensive children, the effect of clonidine therapy on various endocrine, cardiovascular,
and neuromuscular functions has been examined in five male adolescents with idiopathic hypertension. In
studies done before and at the end of 4 weeks of twice-daily clonidine therapy, in an average daily dose of 0.31
mg, no significant effects were noted in the secretory patterns of growth hormone, luteinizing hormone, folliclestimulating hormone, prolac'tin, cortisol, aldosterone, or testosterone, measured in blood obtained every 20
minutes for 24 hours. In blood obtained while the patients were supine and then erect, plasma renin activity and
norepinephrine levels were significantly lowered after clonidine therapy. Cardiovascular responses to dynamic
exercise were little altered beyond a 17% decrease in maximal oxygen consumption. The performance of fine
motor skills was minimally altered. These data provide preliminary evidence that clonidine, an antihypertensive drug that affects the adrenergic nervous system, may not interfere with normal growth and maturation in
adolescent males. (Hypertension 2: 83-89, 1980)
KEY WORDS • adolescents • clonidine therapy
hormonal secretion hemodynamics
• idiopathic hypertension
T
hormones involved in somatic growth and sexual
maturation. Effects of these drugs on growth and
maturation should be determined before they are
given to large numbers of adolescents for prolonged
periods of time.
Clonidine is widely used for hypertension in adults.
Being a centrally acting a-adrenergic agonist, this
drug could affect growth and maturation by altering
the level of hormones whose secretion is influenced by
a-adrenergic mechanisms. Clonidine has been shown
to affect various hormones acutely. After a single intravenous or oral dose of clonidine, growth hormone
rises in various animals 4 6 and normal adult
humans; 7 ' 8 prolactin rises in rats 9 and in adult
humans;10 and stress-induced ACTH secretion is inhibited in dogs.11 Moreover, studies in monkeys have
shown that pulsatile luteinizing hormone (LH) secretion is under the control of a-adrenergic stimulation:
blockade of a-adrenergic tone by phentolamine stops
pulsatile LH secretion.12
Since there are no data available on the effects of
any antihypertensive agent in adolescent hypertensives, and since clonidine is more likely than most
other agents to affect hormonal secretion, we have examined the effects of this drug on various hormones in
five male hypertensives aged 14-16 years over a 5week treatment period. To ensure that the drug would
HE majority of postpubertal hypertensive adolescents with elevated blood pressures are
considered to have idiopathic or essential
hypertension, since their high blood pressures have no
recognizable, reversible cause.1-2 Assuming that the
elevated blood pressure will usually persist, and knowing that untreated hypertension in adolescents may
quickly lead to serious cardiovascular complications,3
we find the use of antihypertensive therapy in such
patients of increasing interest.
The various antihypertensive drugs available have
similar antihypertensive potency, so their suitability
depends mainly on their propensity toward side
effects. In children and adolescents, another factor
must be considered: the effect of the drugs on various
From the Departments of Medicine (Drs. Boyar, Kaplan, Chipman), Pediatrics (Drs. Fixler and Laird), Pharmacology (Dr.
Graham), and Psychology (Dr. Price), at the University of Texas
Southwestern Medical School, Dallas, Texas.
Dr. Boyar died on November 27, 1978.
Dr. Graham is a recipient of a Career Development Award from
the Pharmaceutical Manufacturers Association, Inc.
Supported by U.S. Public Health Service Grant MO1-RR-OO633
and a grant from Boehringer-Ingelheim, Ltd.
Address for reprints: Norman M. Kaplan, M.D., Professor of
Internal Medicine, University of Texas Southwestern Medical
School, 5323 Harry Hines Boulevard, Dallas, Texas 75235.
Received April 25, 1979; accepted July 2, 1979.
83
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HYPERTENSION
84
not interfere with the desire of adolescent boys to
engage in strenuous athletics, we determined the cardiovascular responses to maximal physical exercise.
Since the most frequent side effect of clonidine is
drowsiness, we also assessed the performance of fine
motor tasks. The results show little, if any, alteration
in hormonal secretory patterns, cardiovascular function, and motor coordination. They provide some
assurance for at least the short-term safety of such
therapy in male adolescents.
Methods
Subjects
Five adolescent males with systolic blood pressures
exceeding 140 mm Hg on four separate examinations
over an 18-month period were identified during a
screening program of 10,641 eighth-grade children in
the Dallas public schools.13 These readings were above
the 99th percentile for age in this population. We obtained approval of the Human Research Review Committee and informed consent of the adolescent and his
parent.
The clinical characteristics of the five adolescents
are shown in table 1. They were all well into puberty.
Secondary forms of hypertension were excluded by the
normal results of these procedures: urine analysis;
analysis of serum creatinine, blood urea nitrogen,
sodium,
potassium,
cholesterol, and
urine
metanephrine; assessment of plasma renin activity
while the patient was supine and after he remained upright 2 hours; chest roentgenogram, rapid-sequence
intravenous pyelogram, electrocardiogram, and
echocardiogram.
The adolescents were made to feel comfortable with
the personnel and surroundings by repeated contacts
prior to the study.
Protocol
Pretreatment
Studies
The five adolescents underwent cardiovascular function studies and tests of fine motor skills on separate
days prior to clonidine therapy. Subsequently, they
were admitted to the Clinical Research Center of the
University of Texas Health Science Center at Dallas
for a 24-hour, 20-minute-interval blood-sampling
study with monitoring of the stages of sleep.M That
evening, surface electrodes were fitted to monitor the
electroencephalogram, electro-oculogram, and elec-
VOL 2, No
1, JANUARY-FEBRUARY
tromyogram during sleep. The following morning, a
21-gauge needle was inserted into a forearm vein and
attached to a polyethylene catheter that extended into
an adjoining room. There blood samples were
withdrawn every 20 minutes over the ensuing 24 hours
without disturbing the patient who remained in his
room reading, watching television, eating at usual
times, and sleeping from about 10 p.m. to 6 a.m.
At the beginning of the 24-hour interval, blood
samples were obtained with the patient supine and
twice during quiet standing: after 5 minutes for
catecholamines and after 60 minutes for renin activity.
Thereafter, 5 ml of blood were withdrawn every 20
minutes. The samples were centrifuged immediately,
an aliquot of each combined to form an integrated 24hour pool for assays of cortisol, testosterone, and
aldosterone, and the remainder frozen for assays of
LH, follicle-stimulating hormone (FSH), prolactin,
and growth hormone. A 24-hour urine and blood sample was obtained before and at the end of the study for
measurement of electrolytes, creatinine, and glucose.
The sleep record was scored and the plasma hormone levels plotted against the sleep histogram.
Drug Therapy
After completion of the pretreatment studies,
clonidine was started at a dosage of 0.05 mg at 8 a.m.
and 0.15 mg at 10 p.m. in an attempt to minimize
drowsiness during school time. On weekly visits, the
clonidine dosage was increased by 0.05 mg if the
systolic or diastolic pressures remained above the 95th
percentile for age and if drowsiness was not a
problem.
Posttreatment
Study
After 4 weeks on clonidine, the patients were readmitted to the Clinical Research Center for a second
24-hour study. Drug therapy was continued for
another week, when the tests of fine motor skills and
cardiovascular function were performed. Therapy was
then gradually tapered without incident and the
patients kept under observation,
observation.
Techniques
Hormone Assays
To minimize interassay variability, radioimmunoassays for LH, FSH, growth hormone, and
TABLE 1. Clinical Characteristics of Five Adolescent Males
Case no.
1
2
3
4
5
M
C
T
J
T
Age (yrs)
Height (in.)
Weight (kg)
15 6/12
15 9/12
15 6/12
15 6/12
16 4/12
71 1/2
108.1
90.1
65.8
66
66 1/2
69 1/2
67 1/4
1980
109
72.7
Tanner staging,
pubic hair
IV
ni
rv
rv
rv
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Testdcular
volume (ml)
8
12
15-20
15-20
20
CLONIDINE AND HYPERTENSIVE ADOLESCENTS/5o.yar et al.
prolactin were done simultaneously on all 72 samples
from both studies of each patient. Standards, antibodies, highly purified human growth hormone, LH,
and FSH for iodination were obtained from the
National Pituitary Agency and the National Institute
of Arthritis Metabolic and Digestive Diseases. With
the techniques used,15-'" 1 mlU of LH is equivalent to
3.1 mg LER 907 utilizing LH antibody batch No. 2,
and 1 mlU of FSH is equivalent to 17 mg LER 907
utilizing LH antibody batch No. 4. The intra-assay
variability was 5% to 7%.
Radioimmunoassays for cortisol,17 testosterone,19
and aldosterone19 were done on all 10 integrated
plasma pools. To minimize interassay variation,
radioimmunoassay for plasma renin activity20 and
radioenzymatic assay for plasma epinephrine and
norepinephrine21 were done on the four samples from
both studies of each subject during the same run.
Cardiovascular Function
Echocardiograms were obtained with an Ekoline 20
ultrasonoscope interfaced to an Ekoline 21 strip chart
recorder. Studies were obtained from the third or
fourth intercostal space and the left parasternal edge,
with the subject in the supine position. Dimensions of
the left ventricle, septum, and posterior wall were obtained at the onset of the QRS complex with the ultrasound beam passing through the left ventricle at the
tips of the mitral valve leaflets. For all dimensions, five
consecutive complexes were measured and averaged.
Patients exercised dynamically on a mechanicallybraked bicycle ergometer. A continuous-graded exercise program was used, with the workload starting at
300 kiloponmeters and increased by 300 kiloponmeters every 3 minutes. Blood pressures were
measured using a mercury sphygmomanometer connected to a Narco Biosystems program electrosphygmomanometer (model PE 300), which was
used for semi-automatic cuff inflation. The cuff
covered at least two-thirds of the left arm. Systolic
and diastolic pressures were recorded at the
appearance and disappearance of Korotkoff sounds. A
Frank electrocardiogram was displayed continuously
and the last minute of each work-load level recorded.
Oxygen consumption was measured continuously
using a flow-through hood system.23 Each subject was
urged to continue until complete exhaustion. In no
case was it necessary to stop the exercise tests because
of untoward reactions, arrhythmia, or blood pressures
greater than 240 mm Hg systolic or 130 mm Hg
diastolic. During the repeat-exercise stress test while
on clonidine therapy, all subjects were exercised to
the same work-load level for the same duration of
exercise.
Fine Motor Skills
To assess the possible side effects of clonidine on
perceptual-motor coordination, four tasks were used
85
to represent various levels of cognitive demand on fine
motor skills. The first consisted of 10 trials of a
simple-reaction time task. The second was a choicereaction task, where subjects were required to depress
a microswitch in the presence of one visual stimulus
and refrain from responding in the presence of a second stimulus. There were eight target trials embedded
in a total of 16 experimental trials. For the third task,
subjects were asked to place the tip of a metal stylus as
rapidly as possible in a sequence of 28 holes ranging in
size from 30 to 3 mm in diameter punched in the face
of an upright rectangular easel, without touching the
sides of the holes. The subjects' speed of performance,
number of errors (defined as the number of times the
stylus made contact with the side of the holes), and
duration of errors were monitored electronically. The
final task, designed to evaluate hand steadiness or
tremor, was to place the tip of the stylus in the 3 mm
hole of the easel at a given signal and keep it in place
for 10 seconds without touching the sides of the hole.
During these four tasks, heart rate and basal conductance levels of electrodermal activity were
monitored.
Analysis of Data
The individual values of each hormone measured
every 20 minutes were plotted with the sleep
histogram. The mean values of all 72 samples
collected through the 24 hours were taken to compare
the pre- and post-therapy levels. With the pooled
specimens and the sets of supine and upright values,
the data were compared using Student's t test. Comparison of the scores on the tests of motor skill were
done by means of the Wilcoxon matched pairs signedranks test.
Results
During the 5-week period of clonidine intake, the
patients remained active and in school. Their body
weight, urinary and plasma electrolytes, and glucose
and creatinine clearances were not significantly
changed.
Blood Pressure and Dose of Clonidine
The systolic blood pressure of all five adolescents
was above 140 mm Hg on four examinations over the
preceding 2 years. The average diastolic blood
pressure ranged from 58 to 89 mm Hg. Although these
levels were not inordinately high, they are above the
95th percentile of the large population from which
these subjects came, and the systolic pressure above
the 99th percentile.
Clonidine was started at a dose of 0.05 mg at 8 a.m.
and 0.15 mg at 10 p.m. The dosage was raised at
weekly intervals to bring the blood pressure below the
95th percentile for age (table 2). The mean blood
pressure levels were reduced from 145/69 to 131/67
with a mean daily clonidine dose of 0.31 mg. In three
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HYPERTENSION
86
VOL 2, No
1, JANUARY-FEBRUARY
1980
TABLE 2. Blood Pressure and Dosage of Clonidine
Pretreatment
Blood
pressure*
(mm Hg)
Patient
Case no.
After 2-week
Blood
pressure
(mm Hg)
142/80
148/68
142/67
146/58
148/72
1
2
3
4
5
135/80
136/70
122/66
141/57
120/54
therapy
Clonidine
dose (mg)
a.m.-p.m.
After 4-week
Blood
pressure
(mm Hg)
0.1-0.2
0.1-0.2
0.05-0.2
0.1-0.2
0.1-0.2
therapy
Clonidine
dose (mg)
a.m.-p.m.
0.1-0.2
0.1-0.2
0.05-0.2
0.1-0.3
0.1-0.2
129/76
124/72
135/80
141/56
126/52
•Average blood pressure of four examinations over 2-year period.
patients, moderate daytime drowsiness was noted but
only in one (Case 4) did this preclude increasing the
dose to lower the blood pressure to the desired level.
One patient (Case 5) complained of dry mouth while
on clonidine therapy for the first 2 weeks.
Heart rates did not significantly change, averaging
70.6 before therapy and 65.2 after 4 weeks of therapy.
Although the pattern of growth hormone secretion
was not significantly changed, and there was no consistent temporal relationship between clonidine intake
and the episodic rises in growth hormone, clonidine
therapy did reduce the mean levels of plasma renin activity and plasma norepinephrine in samples of both
the supine and upright patients (table 4). The plasma
epinephrine levels were not significantly changed.
Despite the significant fall in plasma renin activity,
the mean aldosterone level in the plasma pooled from
the 24-hour study period was not reduced.
Hormone Levels
The plasma levels of the various hormones of
pituitary origin (e.g., LH, FSH, prolactin, and growth
hormone) or adrenal origin (e.g., cortisol and
aldosterone) and the hormone testosterone were not
significantly changed after 4 weeks of clonidine
therapy (table 3). Neither the mean levels nor the 24hour secretory patterns of growth hormone (as
measured by samples obtained every 20 minutes) were
altered (fig. 1). The patterns of LH were those typical
of mid-to-late male puberty, u with LH secretory
episodes being greater during sleep than while awake.
Cardiovascular Function
The response to dynamic exercise before and during
clonidine therapy is shown in table 5. Peak heart rates
averaged 188 ± 5.8 after therapy, which is not a
significant change. Peak systolic blood pressures
averaged 208 ± 3.2 and 213 ± 6.6 respectively;
diastolic pressures averaged 58.8 ± 19.2 and
49.6 ± 13.9; so neither systolic nor diastolic pressures
TABLE 3. Plasma Hormone Levels Before and During Clonidine Treatment
Mean 24-hour plasma levels (72 samples)
Case
no.
1
2
3
4
5
FSH
(mm/ml)
Prolactin
(ng/ml)
Mean
Growth
hormone
(ng/ml)
Condition
LH
(mlU/ml)
Control
Treatment
8.9
5.2
10.1
1.6
9.5
10.1
8.4
2.4
Control
Treatment
18.7
20.2
8.4
13.7
16.1
17.2
4.0
Control
Treatment
18.1
18.3
21.9
19.6
8.2
Control
Treatment
10.9
11.0
9.1
11.0
11.5
3.0
8.5
Control
Treatment
10.3
11.1
7.4
8.4
2.8
7.0
8.9
—
15.9
4.3
6.4
2.6
3.0
24-hour plasma levels (pool)
AldosTestosterone
terone
Cortisol
(ng/ml)
(/xg/dl)
(Mg/dl)
1.37
1.66
6.61
7.00
5.8
7.3
2.70
2.57
11.4
10.9
8.0
4.87
5.31
6.7
3.6
9.8
10.7
3.49
3.00
6.3
12.5
13.3
2.36
3.21
11.5
6.5
8.7
5.9
16.3
12.9
Mean
±
SD
Control
Treatment
13.4 =*= 4.6 7.5 ± 1.7
14.0 ± 4.9 9.8 ± 2.9
13.5 ± 5.5 3.6 ± 1.8 2.96 ± 1.31 7.7 ± 2.4
13.1 ± 5.0 4.0 ± 2.4 3.15 ± 1.35 8.6 ± 2.1
Probability values were not significant throughout.
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8.8 ± 5.3
10.4 ± 2.7
CLONIDINE AND HYPERTENSIVE ADOLESCENTS/5o><ar et al.
87
SLEEP STAGES
Awake—i
GROWTH HORMONE, ng/ml
30
oo
20
Z
(4.0 ng/ml)
li
53
10
SLEEP STAGES
Awake —i
REM
I
(4.3 ng/ml)
10-
T*
*~T
0800 1100 1400
I
1
1
P
T
i
1700 2000 2300 0200 0500 0800
CLOCK TIME
FIGURE I. Upper: Case 2. Plasma growth hormone concentration sampled every 20 minutes for 24 hours
after 4 weeks of clonidine therapy. The sleep histogram is shown above the period of nocturnal
sleep. Lower: Control values. The mean values for all 72 samples during each study are given at the right in
parentheses.
showed a significant change. Endurance was unaffected, but oxygen consumption (ml/min/kg) during
dynamic exercise stress fell from an average of
36.4 ± 2.6 to 30.1 ± 2.2 (p < 0.05).
Echocardiographic findings before and during
clonidine therapy in these five patients are shown in
table 6. No significant changes occurred in left ventricular diastolic dimension. Neither the left ventricular shortening fraction nor left ventricular
velocity of circumferential fiber shortening was
significantly affected by clonidine, which suggests that
this antihypertensive agent does not significantly alter
myocardial contractility.
Fine Motor Skills
No changes were observed in the performance of
the reaction-time task, choice-reaction task, and
rapid-sequence-movement task. Following clonidine,
the subjects made significantly more errors on the task
designed to evaluate hand steadiness or tremor, the
mean number of errors rising from 2.25 to 11.2
(p < 0.05). The mean duration of errors also increased
from 205 to 744 msec.
Discussion
Diuretics are likely to be the first drug chosen when
antihypertensive drugs are prescribed for children, just
as they are for adults. If additional therapy is needed,
the next choice is likely to be one of the adrenergic
neuronal blockers that either inhibit the neuronal
release of catecholamines or block their actions upon
the adrenergic receptors. Since the adrenergic nervous
system is involved in the control of hypothalamicpituitary function, these drugs may have various
effects on the secretion of the hormones involved in
somatic growth and sexual maturation. Therefore,
before these drugs are administered for prolonged
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88
HYPERTENSION
VOL 2, No
1, JANUARY-FEBRUARY
1980
Individual Plasma Renin and Caiecholamine Levels and £4-Hour Urine Sodium Excretion Before
and During Clonidine Treatment
TABLE 4.
Case
Norepinephrine
(Pg/ml)
5 mm up
Supine
Renin activity
(ng/ml/hr)
Supine
1 hr up
Urine
Epinephrine (pg/ml)
sodium
Supine
5 min up (mEq/day)
no.
Condition
1
Control
Treatment
3.19
0.95
5.87
2.33
168
227
20
31
268
83
220
7
11
274
Control
Treatment
0.77
0.56
9.43
1.60
118
316
298
223
58
18
20
89
37
185
Control
Treatment
0.62
0.21
1.40
0.38
137
460
11
10
222
68
304
3
15
174
Control
Treatment
1.98
1.09
5.03
1.90
152
463
10
15
135
56
166
3
7
137
Control
Treatment
2.27
0.89
4.07
1.39
301
646
31
41
106
114
477
23
28
149
26 ± 20
11 ± 9
23 ± 12
20 ± 12
206 ± 37
183 ± 24
n.s.
n.s.
n.s.
2
3
4
5
Mean
«±= SD
Control
Treatment
1.77 ± 1.1 5.16 ± 2.9
0.74 * 1.7 1.52 ± 0.7
p < 0.05
p values
p < 0.05
175 ± 74 422! ± 161
82 ± 22 2781 ± 121
p < 0.025
p < 0.025
TABLE 5. Response to Dynamic Exercise
Peak bloodI pressure
Case no.
Peak heart •ate (bpm)
Pretreatment
Treatment
1
200
195
2
200
210
3
190
180
4
180
175
5
184
170
(mm Hg)
Pretreatment
Treatment
196/110
212/0
210/90
214/44
210/50
198/70
220/0
198/74
224/38
216/66
consumption
P e a k o x y g e n consumpti
(ml/min/kg)
Pretreatment
Treatment
30
33
46
36
37
23
28
35
31
33
TABLE 6. Echocardiographic Findings Before and During Clonidine
Case no.
Left ventricular
diastolic dimension (cm)
Pretreatment
Treatment
Left Ventricular
Shortening Fraction (%)
Treatment
Pretreatment
1
4.6
4.4
29
30
2
4.9
4.9
37
41
3
4.2
4.7
28
38
4
5.1
5.4
38
36
5
5.4
5.6
40
38
periods to large numbers of children, studies need to
be undertaken to determine these effects.
In this study, we have found that over a 4-week interval, therapy with the centrally-acting a-agonist
antihypertensive drug clonidine did not alter the secretion of various pituitary, adrenal, and gonadal hormones in five male adolescents. Clonidine was chosen
for this initial study because its major action is that of
a central «-adrenergic agonist and because it has been
Left Ventricular
Vcf (circ/sec)
Treatment
Pretreatment
1.38
1.64
1.12
1.53
1.42
1.33
1.35
1.34
1.19
1.28
shown in acute studies to cause changes in the levels of
growth hormone and other pituitary hormones.4"11
The absence of discernible, significant effects in these
five boys is reassuring, but obviously other adrenergicblocking drugs should be tested in both prepubertal
and pubertal children, whose responses may differ
from these adolescents.
The lack of hormonal effects over 4 weeks of
clonidine therapy differs from the changes seen in nor-
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CLONIDINE AND HYPERTENSIVE ADOLESCENTS/floyar et al.
mal humans and animals given single intravenous or
oral doses. 411 In one study on normal men,' the intravenous administration of 0.15 mg of clonidine induced hyperglycemia in all subjects, maximal at 15
minutes. Despite the hyperglycemia, serum growth
hormone levels rose in eight out of 12 studies. In our
study, neither plasma growth hormone nor plasma
glucose levels were altered at the end of 4 weeks. Since
clonidine was administered over 4 weeks, any acute
changes would have been observed had they occurred.
Therefore, it is possible that such hormonal changes
appear only with the first exposures to the drug.
The patients were receiving pharmacologic doses of
clonidine, as shown by their lowered blood pressures
and reduced levels of both plasma renin and
norepinephrine, a response similar to that in adult
hypertensives given the drug.23' u The significant fall
in plasma norepinephrine is in keeping with the central
a-adrenergic agonist action of the drug to decrease
sympathetic outflow.26 The lower levels of norepinephrine and suppression of adrenergic stimulation
may be responsible for the decrease in renin release.
Plasma epinephrine levels were unchanged, but the
values were at the limit of sensitivity of the assay.
Despite these effects, the cardiovascular responses
to maximal exercise were not altered by clonidine
therapy in these young patients as shown by similar
heart rate and blood pressure responses before and
during therapy. The echocardiographic studies at rest
demonstrated that the indices of myocardial contractility were not altered by clonidine.
Although some daytime sedation was observed,
tests of fine motor skill were little affected by the 4- to
5-week course of therapy. In general, the sedative
effects tended to be maximal at the start of therapy
and diminished with time.
This study is the first to examine the effects of an
antihypertensive drug on the hormonal secretory
patterns and cardiovascular responses to exercise and
motor skills of hypertensive children. Hopefully, additional data on other antihypertensive drugs will be
forthcoming and in children of different ages so that,
when therapy is indicated, it can be given with relative
assurance that normal growth and development will
not be affected.
Acknowledgments
We thank Scott Blackwell, Christy Raimey, Jack Ramsey,
Tamara Segel, Tanya Murray, and Shirley Anderson, R.N., for expert technical assistance; Lindy Legler for secretarial work; and Dr.
W. A. Pettinger for the assays of plasma renin activity and plasma
catecholamines.
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