Interrelationships Among Thiazide Diuretics and Calcium, Magnesium, Sodium, and Potassium Balance in Normal and Hypertensive Man JAY

C

thiaside

FIRONIC

to

diuretic

depletion

nesium

M. SULLIVAN.

and

of

therapy

potassium

retention

and

of calcium

acid in man.’-6 It has intravenous infusion

potassium loss in man,7 use of oral magnesium

as

potassium-sparing

a

on chronic

urinary

with

a history

of

ever,

the

of magnesium

on

calcium

effect

thiazide-induced

and

nesium, and was the main

that re-

hypertensive

take

patients

place if

or the

the

Departments

Brigham Boston,

Hospital, Mass., and

and

blood mag-

balance in man. It of this study to de-

College

of

Medicine,

in part by Grant 8-MO1-FR-31-06 eral Clinical Research Centers Division of Research Resources, tutes of Health, and by grants A. Hartford Foundation and poration. through 530

Computation USPHS Grant

services HL-09495.

Peter

Medical of Tenn. from

Bent

School, Tennessee Supported the

Gen-

Program of the National Instifrom the John the Schering Corwere

normal

in

the

changes

two

and

studied

differences which are

by

potastherapy de-

in blood known to

groups in

to

were

cation

replacement

ac-

balance enhanced

effect

of

the

thia-

zides.

uric

diuretics,

Harvard the University Memphis,

for

Both were

the

magnesium

Material

replacement

Medicine,

replace-

need

how-

potassium,

of

diuretics.

antihypertensive

provided

and

Methods

Twenty-five 12 normal

studies

were

subjects

and

essential hypertension.

out in

carried

13 subjects Ten

with

of the normal

subjects were males and two, females. Their ages ranged from 21 through 25 years.

The

hypertensive

older, with an and

From

the

during

whether response

companied

in

magnesium

patients

termine pressure

pa-

thiaaide

calcium purpose

thiazide

not

formation,8

sodium,

with

has

suppleknown to

oral

eliminate

supplementation

for

calcium

among

pressure,

iuin

has not been studied. study concerns the interre-

acid retention The present lationships

uric

whether would

therapy

levels

stone

termine inent

but the posupplement

Daily dietary oxide are

raise

leads mag-

measure diuretic

yet been explored. ments of magnesium

and

been reported of magnesium

duces tential tients

M.D.. ROBERT G. DLUHY. M.D., WARREN E. C. WACKER. M.D.. HAROLD S. SOLOMON. M.D., GORDON H. WILLIAMS. M.D.. and JOSEPH K. SAMAHA. M.D. Boston Mass., and Memphis, Tenn.

a mean

males

and

taking,

age

were

shown

metabolic tients

ing

females.

examination,

testing,

the renal,

diseases. had

The

95 Journal

and

routine subjects

evidence or

Clinical

pressures mm Hg

of

other

hypertensive

blood 120 of

were history

and

hepatie, The

diastolic

between

On

normal

to be free of any

cardiovascular,

were

of 42 years. Eight

five were

physical

laboratory

subjects

of 29 to 65 years

age range

pa-

rangon at

Pharmacology

THIAZIDES

least

three

separate

tions

while

not

outpatient

receiving

determina-

patients

forms

had

of hypertension

taking,

physical

quence

intravenous

urinary or

of vanillylmandelic

metanephrines,

of

heart

function

failure

Research

Brigham ad

clearance. admitted to the of

1-lospital

rates were

measured

the

position

supine

upright All

stant, mEq

isocaloric sodium,

mg ml

subjects

study who

intake

placed

on diets

a period of 12 urine collections measurement acid, total

chloride,

C02,

calcium,

acid, protein, and of each four-day renin

activity

trations

and

were and

position tion,

and

subjects

a 10

mEq

per

after

measurement sodium, potassium, phosphorous,

angiotensin four

the

hours

of

glucose

were

measured.

rates

were

Noveniber-December

day.

uric

ambulaelecon

mg

for a period measurements of the

The of been

of 12th

magnesium 100 mg was

established

excretion

that of

mag-

during

the

administration

of

diuretic

was

approximately

100

B. Two

subjects

mg/24

hr.

Group identical

manner

magnesium study

period

same

changes

sence

of

C.

to determine

of

with

the

normal

and

ab-

effect

of

in

re-

oxide

be-

the

magnesium

during the

the

subjects

magnesium during

period assess

third

whether

agents

administered

chlormethiazide to

of

the

magnesium. Four

order,

study

in

take place in the

pharmacologic

versed

studied addition

during

would

added

received ing

were

without

supplement

second plus

the

third

order

of

tn-

period, adminis-

tration. 13

The

Group studied

hypertensive

patients

1).

of

Seven

the

patients

at the end of a four-day

equilibration in On trichlormcthiazide

plus

were

as follows:

100

another

Aldos-

100

in addi-

the hospital, then for four days

measurements

mg

magnesium

four-day were

period repeated

were

period

end of which measurements were They were themi placed on thiazide

supine

measured

on

mouth

morning

urinary

days,

repeated.

placed by

the

it had

average

studied

the end plasma

and

terone

the same

of

II eoncenin

trocardiograms secretion

uric

ereatinine, and were obtained

magnesium. At study period,

blood

for

potassium,

measured

fasting

day

maintained

after

Group

Twenty-four-hour made daily for

magnesium, Blood samples

then daily

on

four

were

nesium

entire

three

were

for

their

2000

for

days. were

every other day hematocrit, creatinine,

100 100

and

repeated

an

contained potassium,

of

on

a period

thiazide

in the a con-

for

of sodium,

calcium, volume.

in

end

to triehlormethiazide days, and the ba.seline

the

on

calcium,

daily

except

diet. All

sodium

mg

were oxide

placed for

the

selected

measured

placed

diet which 100 mEq

period, were

5 minutes

At

Cliniwas

The 12 as fol-

were

measurements

subjects

tion four

subjects

day of hospitalization. supplementation dose

pulse

2 minutes

were

100

fluid

after

was

days.

baseline

were

Bent

and

Weight

magnesium, total

Peter

pressure and

Position.

daily.

the

Six

or by

for study. Activity

Blood

lihitum.

impaired

urinalysis

Center

of

of equilibration. were then treated

trichlormethiazide

eight

The

evidence

or

by routine

endogenous ereatinine The patients were cal

had

A.

b.i.d.

magnesium

None

subjects

congestive

renal

acid,

determination.

hypertensive

of the

17-hydroxysteroids,

17-ketosteroids

the

se-

24-hour

the above measat the end of a

lows: 4 mg

rapid

pyelogram,

period subiects

Group

on history

examination,

values for all were obtained

four-day normal

of secondary

revealed

excretion

total

agents were weeks prior to of the hyper-

evidence

MAGNESIUM

Control urements

antihypertensive

agents. All antihypertensive discontinued at least three admission for study. None tensive

AND

oxide

repeated. diuretic daily

after for

of

placed at the

the

for

which third

time. 1978

531

SULLIVAN,

Group E. Three patients at the end of the four-day and

then

daily

started

for

ceiving

an

on

were control

100

eight-day

diuretic

mg

studied period

magnesium

period

without

mg

three sodium

of magnesium system when

oxide

Magnesium renin

activity

renin

activity

tration described

and

was

method

renin

EDTA

tion at renin

25#{176}Cfor

tration.

Blood and by

II

of

ranged

from

to

different

concentrations. computer

analysis nificance

of data. using

variance

with

formed

between

analysis

within

for

more or

cant.’3 This Studies 532

less

per

by

factors factors,

regimens.

was

test

detailed

analysis.

were

considered

sigof per-

and

one

testing

for

a was

Newman-

P

was

Committee

approved

values

of

by the the

Peter

diuresis

(10.2

five

diastolic

below

diastolic

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535

SULLIVAN,

DL UHF,

WACKER,

ET

AL.

CLI

t

8

a

a a

8

a

‘iq.

1.

Daily

pressure, balance seven,

variations

hypertensive

thiazide

diuretics

and

JIfq2+

in

response

subsequent received

100

mg

to

a 100

fell

by 2.8

per

group

and

normal not

group change

day period cliuretirs also

cent

(P

2.3

per

(P