Blood Pressure Response to Norepinephrine Infusion in Relationship to Plasma Catecholamines and Renin Activity in Man NICOLAS
B
both
ECAUSE
and
norepinephrine
sympathetic
vasoconstriction and has been speculation epinephrine hypertensive mine
metabolites
or
reports
failed
plasma
catecholamines
been
when
studied.7’8 It has
been
reported
low,3
to show
tension
uniformly
recent elevated
in essential
shown
for
many to
were
years
that
various
stim-
uli9’4 sion.
is increased in essential hypertenBoth the intravenous and intraar-
terial were
administrations associated with
cular
reactivity
sion,
but
not
However, doses
in are
weight,
the
Dr.
Medicine, University Cal. This Meetings
Pharmacology,
although kilogram
concentrations was
not
California, School
of
Vlaehakis Division
to
ex-
Cal.,
New
Professor Pharmacology,
and
York, of
effect blood
activity
There
clinical
data
are
less that,
than 140/90 mm Hg without treatment,
used.15 eases,
laboratory
and
blood
multichannel
chemistries,
and test.
were
graded scale.
ventricular
Patients
with heart Journal
urine
Changes For
scoring renal
evalua-
Clinical
the
system
was
or hepatic
dis-
disease, of
in
according
hypertrophy
Estes
ischemic The
x-ray,
complete
metabolite fundi
left
chest
urinalysis,
Keith-Wagner of
hyper-
procedures
pyelogram, blood
ocular
tion
were
many above the last 12
Sustained
and
routine
Rombilt
when
readings
present when blood pressure was greater than 140/90 mm testing consisted of physical
sequence
the
in Table
present
and in
electrocardiogram,
count,
to
pressure
observation.
examination
the
examined.
presented
or more
tension was consistently Hg. Routine
plasma
15 patients with hypertension. was
blood
into
and
was
were primary
one
including
its and
norepinephrine
pressure
hypertension
of
in
divided
of
(PRA)
Group I. uncomplicated
months
and
subjects
subjects,
upon
Their
hypertensive
Methods
the
I. Labile
Cal.
catecholamines
twenty-five groups,
renin
Los Angeles,
activity.
and
In
in
plasma
catecholamine
Clinical California, Los Angeles, work was presented in the National of the American College of Clinical Washington, D.C., April 1977.
of Southern
Material
automated
University
Los Angeles, Medicine,
renin
rapid
measured. to norepi-
Medicine,
is Associate of
admin-
designed
responsiveness of
drug of body
of
were
Departments
vas-
hyperten-
hypertension.’#{176}
per
study
vascular
of Southern Mount Sinai
654
renal studies,
calculated
present
amine
N. Y.
essential
catecholamines
The
From
with these
plasma
istered
of norepinephrine an increase in
with
plasma
infusion
hyper-
groups
reactivity
to
two
F.C.P.
normotensive
relation
as
while
age-matched
neurovascular
there of nor-
M.D..
infusion
age-matched
hypertension. In urinary catechola-
have
elevated,
nephrine
produce
hypertension, about the role
in essential patients
normal,
infusion1
stimulation2
D. YLACHAKIS.
congestive Pharmacology
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VLA CHA XIS
heart
failure,
thyroid
bradycardia,
or
were
excluded
ous
medication
three
from prior
of
II.
53
1.7
of
procedures
gram,
complete
alysis,
and
blood The
written
in
was
the
and
on
the
A
5%
every to
an
in the
was
per
to
for
of
at a rate
infusion turned 656
At
a period (baseline),
and
Labs,
or
of
period and before off, blood was again
Houston, weight
In and
was for
Peuler’T
plasma norepiare converted catechol-O-methyl-
5-adenosylmethionine3H-normetanephrine
and
assay
The
is less
than
sensi-
1 pg
nor-
and epinephrine, and the test 50 jl or less of plasma. The dayvariability
cent
the
norin the
Johnson18
respectively.
the
cent The
and and
enzyme to
to-day per
Passon
Peuler
and
for
assay
this method epinephrine
purified
of
com-
angiotensinase method
by by
transferase
of
for for
the
assay
norepinephrine
average
blood of
pressures
seven baseline
and
phrine
infusion
periods.
The
urement
was
analysis
Student’s
disregarded.
i-test,
group.
also
determined. The
the for
Correlation
Journal
For
i-test
between
paired
represent
measurements
during
same
±1.2 ±3.8
epinephrine.
reported
comparisons
is and
tained
the
15-minute
the pump collected
by the
ac-
during
plasma
epinephrine
developed modified
was used. nephrine
renin
enzyme.16 and
plasma
determined
Plasma
radioenzymatic
epinephrine and
of
radioimmunoassay
generated of
converting
per
and norepinevia an infu-
the
I
estimation and potassium.
were
by
inhibition
(within
was obtained starting the
for
Mass.).
angiotensin
epinephrine requires
she
and then
(Instrumentation
assessed
tivity
of 15 blood
body
was
until plasma
centrifuge
collection subjects,
potassium
Lexington,
auto-
was
ice
the
20#{176}Cand
-
testing, sodium
and
was reobtained
in
and
photometry
3H-metanephrine,
catecholamines
of 0.1 pg/kg
of
flame
of
urine the
the
3H-methyl
conversahe
of
open.
subject
avoid
plasma
end
norsam-
an
Instruments. the
left
solution
by
testing unless to report.
(Texas
minute.
Sodium
A new
(Arteriosonde Inc., Nutley, The
and
the
for blood
recorded
2 minutes. relax
withdrawn
Texas),
in
kept
at
was
period, strip The
a cold
freezer
before excretion
and
of
in
the
A 24-hour from each
the
asked to cathe-
water
device Roche,
completion of relaxation
pump
in
the
rate
each
thawed and promptly analyzed two weeks of its collection).
plete
diet.
catheters
and PRA determination, phrine infusion was started sion
separated
kept
the
3 hours
one
were testing,
was
obtained
unrestricted
and
keep
during the any complaint
After minutes was
after
dextrose
pressure
advised tion had
of
was
subject was two indwelling
matically inflated 1216, Hoffmann-La N.J.)
estimation
right
to
were
during
Heart
of
of
end
by
each
studies
vein, were inserted infusion and for
used
Blood
from
blood
the and
in
antecubital epinephrine pling.
of
PRA.
end
specimens
the
day the
informed,
laboratory
position,
Subsequently, lie on a bed,
was
nature and
For
sitting
one
urinblood
obtained
profile,
ambulation,
ters,
routine
infusion in
renin
the
count,
experimental
hours.
plasma
labo-
the
in some subjects an ECG corded during both periods.
tivity
out
morning
and electrocardio-
explained,
consent
con-
multichannel
subject. Norepinephrine
ten the
testing
examination
was
least
were seven a mean age
including
and at
blood
There with
automated
testing
previat
Routine
physical
chemistries.
All
eatecholamines measured
group included age matched with
years.
ratory
carried
study.
withdrawn
subjects. three female
±
sinus
tachycardia
to testing.
This
sisted
the
the
volunteers
hypertensive male and
of
was
weeks
Group healthy
abnormalities,
history
obnorepine-
first
statistical
was two
changes
used groups within
coefficients
of
Clinical
meas-
Pharmacology
for and the were
BLOOD
PRESSURE
RESPONSE
TO
NOREPINEPHRINE
Results Hemodynamsc
Changes
to Plasma In
the
phrine
increased to
2006
fusion; and norepinephrine pg/mi
in
at
the
the
of
two
values
in
Hg,
with
Hg,
and
the
creased
an
pressure
of
15 ± group
increased
by
A
blood pres12 and 69 ±
5 mm
pressure
in-
29
mm
1.6
mm systolic
Hg.
In blood
to
mm
Hg,
10
‘4...
I
70 4
60
Hg,
32
with
DIASTOLIC
BLOOD
PRESSURE
mean
21.4
the
oE C
blood
#{149}
.
#{246}:#{246}
Hg,
mean
from
the
8.3
or
there
was
NORMO-
Fig. 1. Mean diastolic blood and hypertensive ence between
HYPERTENSIVE
7.3
the
increases
in
both
0.6
beats/min
change
was
±
1979
(A)
±
=
0.42,
1.1 beats/ and
by
normotensive. in both
groups
both), but the difference was not significant. There
correlation and
the
during a posi-
between
blood
pressure
heart change
rate in both
groups. Changes
Plasma
HYPERTENSIVE
In and
in normotensive (.) subjects. The differthe two groups was significant at P value less than 0.025 for the change in systolic and 0.01 for diastolic blood pressure. pressures
no
(r
group in
was
plasma
age
significant
for groups
(.0