Heterogeneous the salt-sensitivity Friedrich
C Luft
and
Myron
ABSTRACT
Blood
creases
in dietary
salt
tensive
individuals,
tion
are
whereas
in still
restriction.
and
involve
and
the
may
also
others,
play
mellitus.
sensitive
genetic
aldosteronism
and
volume
Liddle to
maneuvers
genetic
sensitive
and
but
if the
techniques Am J Cliii KEY
and
cannot
essential
putative
gene
WORDS
Short-
used
to
on a large
are
not
yet
tivity
scale.
three
saltavail-
identified,
trial-and-error
salt
such
show
age, and However,
a convincing
in blood salt-blood and noted
have
effect
between
that
salt
intake
with of hyfailed to
on alterations
many
studies
in the
were
amount
diminished
relatively
of salt
ingested,
or
normotensive
susceptibility
a genetically
predisposed
to
of the
hypothesis
short,
did
and
not
were
have use
conducted
individuals
pressor
sensitivity
effects to
large
the
with or
paradigm
that
may
pothesis with the data vary in their responses 6125
reconcile
random
the
blood
of individsensitivity
also
and
explain
the
observed
in re-
variability
pro-
and
Grobbee
the
salt-blood
pressure
available is the proposal to alterations in salt intake Am
J C/in
of hy-
that humans with respect Nutr
(5)
criticized
methodobogic grounds. fatal flaws frequently made
the
most
common
tion
(Figure
tion
of
of which
1). The
salt
is the
post
sensitivity
hoc
have
of salt
of the
normal
distribu-
of an arbitrary pitfall
of
to the
mean.
defini-
confusing
pressure measurements Blood pressure tends measurements in many
regression
sensi-
attention to in this area,
The
the
with salt to decrease subjects, a “white
coat”
pressure elevation evoked by the stress of a physician) generally does not dissipate is in the absence of a concurrent, placebo-
multiple
(6).
measurements
theoretical
although
the initial However,
to minimize
occurs
deleterious
blood
“might
pressure
help, may
potential,
flaw
a desirable
restriction (the
notion
study other the
of salt studies
effect
of this
(7).
A second that
in the
control group. Interestingly, suffered from this flaw
used
factor
flaw
selection
results
termed
the
Watt (4) drew by investigators
in salt-sensitive pressure can’t
occur
the
is engendered
decrease
hurt”
phenomenon
patients,
there
in
argument).
assumption with cannot
salt-resistant Because
patients of
the
pressure
increase
in some
by
in blood
and
salt-resistance
patients
a rise
could
salt be
thus requires
in blood have
risk
further
study.
who
effects
salt. A
(4)
sensitivity
dietary
pressure
and complications studies have often
Proponents
borderline-hypertensive
lacked
in blood
of reduced
controversial.
differences possible
a link
increases
the prevalence interventional
although
on
phenomenon
hypertension,
suggested
pressure,
values
that and
EXIST?
variation of blood sensitivity of blood pressure. with time and with repeated
pressure. Because of these discrepant observations, the pressure hypothesis has been vigorously debated
remains
in
studies blood
pressure
SENSITIVITY
random
methods.
sensitivity,
SALT
treated
and
could
blood
Were
intake
Salt
re-
pressure
composed
increases
diet, explanation.
a reduced-salt
do not.
responses.
pressure of
in blood salt
a population
Termed
individuals
increase
dietary
varied
phenomenon (blood having to deal with with time. The error
Epidemiologic increasing pertension.
within
these
alternative
Watt
identhese
with
are
DOES
diet
intake
to
between
exist
distribution
an
some
individuals)
relation
to blood
an
with
(salt-resistant
would
sponse
INTRODUCTION
salt
intake
( 1-3).
pressure that
dietary
individuals
hypertension
salt,
salt
exhibiting
blood
salt-
however,
polymorphisms
Sodium,
be
be used
may replace the current Nutr l997;65(suppl):6l2S-7S.
nutrition,
implies
simple
pressure
vides
identified.
may
for identifying
salt-resistant
is increased
longer-term
individuals;
and
others
no
normal
diagnosed
been and
reproducible
techniques
that
resistance
predisposition
readily
and
uals
electrolytes,
and
notion
glucocorticoid-remediable
have
salt-resistant
with
acquired
balance
this
to a high
case,
non-insulin-dependent
contraction
are cumbersome
Molecular able.
be
and
as
syndrome, and
appear
salt-sensitive
Genetic
but
such
with
increase
of other
with
uncommon
expansion
interventions tify
Some
intake:
fluid
sensitivity,
spond
occurs,
partly
salt sensitivity
in persons
syndromes.
achieved
to extracellular salt
restric-
pressure
are
medications.
de-
hyper-
salt
actually
the intake
role because
and
that
responses
of age,
a substantial
with
in blood
may
and
In some
approach
pressure
of certain
individuals
increases
pressure
no change
heterogeneous
the influences
to
heterogeneous.
and or
blood
The
diabetes
term
significant
influence
black
in
responses
are
in blood
little
salt
1997;65(suppl):612S-7S.
I From the Franz Volhard Clinic, Rudolf Virchow University Hospital, Free University of Berlin, and the Hypertension Research Center, Depart-
ment 2
of Medicine, Address
Strasse
50.
Indiana
reprint 13122
Printed
University
requests Berlin,
in USA.
to FC Germany.
© 1997
School Luft, E-mail:
American
of Medicine,
Franz
Volhard
Indianapolis. Clinic,
Wiltberg
[email protected]. Society
for Clinical
Nutrition
a
Downloaded from www.ajcn.org by guest on July 13, 2011
salt
pressure
intake
In others,
in dietary
H Weinberger
decreases
clinically
medication.
responses to changes paradigm1’2
THE
SALT-SENSITIVITY
PARADIGM
61 3S
Frequency (%)
-7
-6
-3
-4
-5
-2
Change FIGURE
1. Hypothetical
80 mmol/d
over4
pressure)
divides
chance
only
The
the
group
if data
A third
from
faulty
measured
equated
by
tends
sensitivity protocol
of used
mation are
subgroups
randomized,
the
are
different
presblood
in a group
mm
Hg)
and
from
one
Four
protocols
blood salt
only when the reproducible infordesigns
There
was
blood
pressure
have
been
volume
depletion,
both,
support
dietary
intravenous lowed
saline
conducted pressure ume
changes
also
showed
They
that
In
study
the
this
pressure
(Figure
compared salt
pressure 2)
(10).
two
previous were
protocol
and
were
and
adrenal
of
blood
on
> 700
protocol
was
with protocol
had
repeated
in
the
advantage
of avoiding small
number
salt
investigators
with
between dietary
20()
from
random
permission
(4).
the salt
to
in blood
response
intake
of
in
both
able
some
diet
that
pressure
of 5 mm
resistance.
number was
four
of subjects
and
salt
not
renal report
and
used
volume
with
degree
means
to identify
of
pressure
is
accord exists and a longer
definition useful
of repro-
definitions
of blood
a clinically
practical
Hg
is termed twice in a
differing
sensitivity
the
salt
a 5-mm
salt intake, performed
and that a statistical loading and depletion and
to define by
a significant
Nevertheless,
arbitrary
as a clinically been
salt
was
high was
(15). protocols, that
intervention.
twice
in the
men and women in random order. A
indicated
pressure with This protocol
described divergent
remains
Hg
Resistance,
suggest
subjects did
of
does In a
however.
et al (14) studied normotensive 20 or 300 mmol NaCl/d for I wk
blood
also diet.
nonmodulators
investigators
to manipulation
subjects,
in
a diuretic.
concordance
( 1 2). These
responses
or
and
of these
a significant
responses
in whom
appropriately
et al ( 1 3) found
a reproducible phenomenon between short-term volume
well
patients
increase
patients (nonmodulators) in response to a high-salt studied
to show
in blood
dietary
not
of salt
sensi-
definition, it, have
as not
as
found.
volume
correlated in response only
techniques in
to a
published for
pressure
order
from
is distinguishable
II or to a low-salt
They
sensitivity,
yet
is the
of
intake
or increase
hypertensive did
Hollenberg
in these
limited
these
the
the
DEMOGRAPHIC WITH
effects
subjects
and
CHARACTERISTICS
SALT
ASSOCIATED
SENSITIVITY
assame
(I 1) studied normotensive medical students placebo-controlled dietary protocol. This
a relatively
studied rate
pressure
Race
and
age
and
others
We et al a randomized,
salt
Reproduced
in
secretion
decrease in counterregulation.
subjects and blood with salt and vol-
persons.
Sharma
no change.
correlation
flow in these appropriately
sensitivity
tivity
observed This
their
Hg.
response
et al (12)
study
These fol-
to the
this
changes
salt-sensitive.
ducibility
to achieve
significantly
different
responses
expansion
response
was
is
reproducibility. protocol involving
This
study
of
pressure
furosemide
subjects.
blood
in blood
diet of
and
performed
protocol
changes
to have
sessment
a combination
7
reduced
mm
reproducibility.
and
Renal blood not increase
change
in salt-
once. These and salt and
volume
diet
a subsequent
expansion-contraction the
to achieve
hypertensive
used
of blood
within 12 mo in additional correlated significantly
(9).
low-sodium
or
sensitivity
of a low-salt
and twice responses
salt
loading
contraction.
normotensive
that
were
on the basis of observed al (8) used a short-term
by provision
volume
that
However.
-5
a significant
Ruppert receiving
more than salt loading
interventions,
the notion
a real phenomenon Weinberger et
with
reported subjects acute
6
who
(
