- Email: [email protected]
PARADOXICAL EFFECT OF SODIUM RESTRICTION ON BLOOD PRESSURE IN PEOPLE ON SLOW-CHANNEL CALCIUM BLOCKING DRUGS
793
Letters
to
the Editor
PARADOXICAL EFFECT OF SODIUM RESTRICTION ON BLOOD PRESSURE IN PEOPLE ON SLOW-CHANNEL CALCIUM BLOCKING DRUGS
SIR,-We describe here a study of dietary sodium restriction in patients attending a hypertension clinic, in which patients benefited by having lower blood pressures unless they were taking a slowchannel calcium blocking agent. We studied patients who had been attending a hypertension clinic for at least three months, who were taking only one drug or no not been altered for 2 months. The advised by a dietitian to reduce their sodium intake. They were then seen three further times, 2-4 weeks apart, and the dietary advice was reinforced at least once and more frequently if deemed necessary from the urine electrolyte excretion. The aim of the dietary advice was to reduce 24 h.urinary sodium to 50-70 mmol. The patients were weighed; blood pressure (BP) was measured in triplicate on a ’Dinamap’ automatic recorder after 10 min lying and 5 min standing (the mean of the second and third readings being used); 24 h urine collections were analysed for sodium, potassium, and creatinine. Post-diet urine, sodium, and potassium excretion were corrected for any difference in urinary creatinine (Cr) excretion by multiplying the measured urinary sodium by (pre-diet Cr/post-diet Cr). 78 patients were studied: 10 were on no treatment, 10 were taking a diuretic (thiazide, frusemide), 10 were on centrally acting drugs (methyldopa, clonidine), 22 were taking a 0-blocker, and 16 were on slow-channel calcium blocking drugs (verapamil, nifedipine); 10 patients (controls) were reviewed just as often, but were not seen by the dietitian and were on a thiazide or a P-blocker only. The six groups were similar, except that the group on no treatment and the group on centrally acting drugs had a higher initial BP. In the controls there was no significant alteration in BP or electrolytes while in all diet-advised groups the 24 h urine sodium fell, with no significant alteration in potassium. Weight fell too, but less in the patients on slow-channel calcium blocking drugs than in the others. BP fell significantly in all patients given dietary advice except for those on calcium blocking agents, in whom supine diastolic BP rose (table, figure). In 18 of the 68 patients placed on a reduced sodium intake, BP rose and 12 of these 18 patients were on slow-channel blocking drugs. If all patients were included there was no relation between change in urine sodium excretion (x), and change in BP (y), but if the patients on slow-channel calcium blocking drugs were excluded, there was a significant correlation
drugs, and whose therapy had patients
were
(y=2-78+0-04x; r=0-38, p<0-05). These results confirm our observations that sodium restriction reduces BP in hypertensive patients. 1,2 However, patients receiving slow-channel calcium blocking drugs differed significantly from all other patients, in that the BP did not fall and supine diastolic BP rose.
diastolic randomisation.
Supine
BP
in
different
groups
before
and
after
Co=control, N=no drugs, D=diuretic, B=&bgr;-blocker, Ca=slow-channel drugs. SEM indicated.
calcium blocker
action of sodium restriction and slow-channel calcium blocking drugs. If excess sodium causes BP to rise by activating a cellular mechanism that causes an increase in an important component of cellular calcium in vascular smooth muscle with a supposed increase in arteriolar vasoconstriction, 7,8 sodium restriction might reverse this effect. Slow-channel calcium blocking drugs, by interfering with calcium entry might also reverse this effect and thus the effects of the two therapies would not be additive. This study supports the view that sodium restriction will reduce BP in people with hypertension, but emphasises that the effectiveness may be altered by the drugs the patient is receiving. The support of the National Health and Medical Research Council and the Australian Department of Veteran Affairs is acknowledged. The study could not have proceeded without the help of the nurses and the cooperation of the
patients. Department of Physiology, University of Melbourne, Parkville, Victoria 3052, Australia; and Hypertension Clinic, Repatriation Hospital, Heidelberg, Victoria
TREFORMORGAN ADRIENNE ANDERSON DIANE WILSON JOHN MYERS JUNE MURPHY CARYL NOWSON
Morgan T, Gillies A, Morgan G, Adam W, Wilson M, Carney S Hypertension treated by salt restriction. Lancet 1978; i: 227-30 2 Carney S, Morgan T, Wilson M, Matthews G, Roberts E Sodium restriction and thiazide diuretics in the treatment of hypertension Med J Aust 1975, i: 803-07 3 Christensen, CK, Lederballe Pederson O, Mikkelsen B Renal effects of acute calcium blockade with nifedipine in hypertensive patients receiving beta-adrenoceptorblocking drugs Clin Pharmacol Ther 1982, 32: 572-76 4. Sluiter HE, Huysmans F Th M, Thien TA, van Lier HJJ, Koene RAP. Haemodynamic, hormonal, and diuretic effects of felodipine in healthy normotensive volunteers. Drugs 1985, 29 (suppl 2) 26—35 5. Gross F. Drugs acting on arteriolar smooth muscle (vasodilator drugs). In Gross F, ed. Antihypertensive agents Berlin Springer, 1977 397-476. 6 Koch-Weser J. Vasodilator drugs in treatment of hypotension. Arch Intern Med 1970; 1
133: 1017-19
There
several possible explanations. Despite acting as vasodilators, slow-channel calcium blocking drugs do not cause weight gain.3,4 Retention of sodium with concomitant weight gain occurs with many antihypertensive drugs,’’6 and this is one reason why diuretics are useful additives to most other antihypertensive drugs. A finding that the response to sodium restriction is small in the absence of sodium retention is not, therefore, surprising. Another explanation may be that there is a common mechanism of are
CHANGES IN WEIGHT AND BLOOD PRESSURE
7 Blaustein MP. Sodium ions, calcium ions, blood pressure a reassessment and a hypothesis Am J Physiol 1977,
regulation and hypertension: 232: C165-C173.
8 de Wardener HE, MacGregor G Dahl’s hypothesis that a saluretic substance may be responsible for a sustained run in arterial pressure Its possible role in essential hypertension. Kidney Int 1980; 18: 1-9
LOW-DOSE DOXAPRAM FOR APNOEA OF PREMATURITY
SIR,-Doxapram has been proposed for the treatment of idiopathic apnoea in premature babies when methylxanthines have failed. Usually the two drugs have been given together.l-3 Since small doses of doxapram have a selective action on ventilatory drive and since larger doses can cause central-nervous-system toxicity (eg,
convulsions)4,5 we decided to try doses lower than those previously
’p<0
os, tp
1 (pained t tests).
proposed. In a pilot study doxapram was given intravenously at a dose of 0. 25 mg kg-1h-1(6 mg/kg daily) instead of 2 - 5 mg kg-11 h- 1. All infants (see table) had at least six daily episodes of recurrent idiopathic apnoea lasting 15 s or more with a heart rate below 80/min despite treatment with caffeine (10 mg/kg loading dose and
Letters
to
the Editor
PARADOXICAL EFFECT OF SODIUM RESTRICTION ON BLOOD PRESSURE IN PEOPLE ON SLOW-CHANNEL CALCIUM BLOCKING DRUGS
SIR,-We describe here a study of dietary sodium restriction in patients attending a hypertension clinic, in which patients benefited by having lower blood pressures unless they were taking a slowchannel calcium blocking agent. We studied patients who had been attending a hypertension clinic for at least three months, who were taking only one drug or no not been altered for 2 months. The advised by a dietitian to reduce their sodium intake. They were then seen three further times, 2-4 weeks apart, and the dietary advice was reinforced at least once and more frequently if deemed necessary from the urine electrolyte excretion. The aim of the dietary advice was to reduce 24 h.urinary sodium to 50-70 mmol. The patients were weighed; blood pressure (BP) was measured in triplicate on a ’Dinamap’ automatic recorder after 10 min lying and 5 min standing (the mean of the second and third readings being used); 24 h urine collections were analysed for sodium, potassium, and creatinine. Post-diet urine, sodium, and potassium excretion were corrected for any difference in urinary creatinine (Cr) excretion by multiplying the measured urinary sodium by (pre-diet Cr/post-diet Cr). 78 patients were studied: 10 were on no treatment, 10 were taking a diuretic (thiazide, frusemide), 10 were on centrally acting drugs (methyldopa, clonidine), 22 were taking a 0-blocker, and 16 were on slow-channel calcium blocking drugs (verapamil, nifedipine); 10 patients (controls) were reviewed just as often, but were not seen by the dietitian and were on a thiazide or a P-blocker only. The six groups were similar, except that the group on no treatment and the group on centrally acting drugs had a higher initial BP. In the controls there was no significant alteration in BP or electrolytes while in all diet-advised groups the 24 h urine sodium fell, with no significant alteration in potassium. Weight fell too, but less in the patients on slow-channel calcium blocking drugs than in the others. BP fell significantly in all patients given dietary advice except for those on calcium blocking agents, in whom supine diastolic BP rose (table, figure). In 18 of the 68 patients placed on a reduced sodium intake, BP rose and 12 of these 18 patients were on slow-channel blocking drugs. If all patients were included there was no relation between change in urine sodium excretion (x), and change in BP (y), but if the patients on slow-channel calcium blocking drugs were excluded, there was a significant correlation
drugs, and whose therapy had patients
were
(y=2-78+0-04x; r=0-38, p<0-05). These results confirm our observations that sodium restriction reduces BP in hypertensive patients. 1,2 However, patients receiving slow-channel calcium blocking drugs differed significantly from all other patients, in that the BP did not fall and supine diastolic BP rose.
diastolic randomisation.
Supine
BP
in
different
groups
before
and
after
Co=control, N=no drugs, D=diuretic, B=&bgr;-blocker, Ca=slow-channel drugs. SEM indicated.
calcium blocker
action of sodium restriction and slow-channel calcium blocking drugs. If excess sodium causes BP to rise by activating a cellular mechanism that causes an increase in an important component of cellular calcium in vascular smooth muscle with a supposed increase in arteriolar vasoconstriction, 7,8 sodium restriction might reverse this effect. Slow-channel calcium blocking drugs, by interfering with calcium entry might also reverse this effect and thus the effects of the two therapies would not be additive. This study supports the view that sodium restriction will reduce BP in people with hypertension, but emphasises that the effectiveness may be altered by the drugs the patient is receiving. The support of the National Health and Medical Research Council and the Australian Department of Veteran Affairs is acknowledged. The study could not have proceeded without the help of the nurses and the cooperation of the
patients. Department of Physiology, University of Melbourne, Parkville, Victoria 3052, Australia; and Hypertension Clinic, Repatriation Hospital, Heidelberg, Victoria
TREFORMORGAN ADRIENNE ANDERSON DIANE WILSON JOHN MYERS JUNE MURPHY CARYL NOWSON
Morgan T, Gillies A, Morgan G, Adam W, Wilson M, Carney S Hypertension treated by salt restriction. Lancet 1978; i: 227-30 2 Carney S, Morgan T, Wilson M, Matthews G, Roberts E Sodium restriction and thiazide diuretics in the treatment of hypertension Med J Aust 1975, i: 803-07 3 Christensen, CK, Lederballe Pederson O, Mikkelsen B Renal effects of acute calcium blockade with nifedipine in hypertensive patients receiving beta-adrenoceptorblocking drugs Clin Pharmacol Ther 1982, 32: 572-76 4. Sluiter HE, Huysmans F Th M, Thien TA, van Lier HJJ, Koene RAP. Haemodynamic, hormonal, and diuretic effects of felodipine in healthy normotensive volunteers. Drugs 1985, 29 (suppl 2) 26—35 5. Gross F. Drugs acting on arteriolar smooth muscle (vasodilator drugs). In Gross F, ed. Antihypertensive agents Berlin Springer, 1977 397-476. 6 Koch-Weser J. Vasodilator drugs in treatment of hypotension. Arch Intern Med 1970; 1
133: 1017-19
There
several possible explanations. Despite acting as vasodilators, slow-channel calcium blocking drugs do not cause weight gain.3,4 Retention of sodium with concomitant weight gain occurs with many antihypertensive drugs,’’6 and this is one reason why diuretics are useful additives to most other antihypertensive drugs. A finding that the response to sodium restriction is small in the absence of sodium retention is not, therefore, surprising. Another explanation may be that there is a common mechanism of are
CHANGES IN WEIGHT AND BLOOD PRESSURE
7 Blaustein MP. Sodium ions, calcium ions, blood pressure a reassessment and a hypothesis Am J Physiol 1977,
regulation and hypertension: 232: C165-C173.
8 de Wardener HE, MacGregor G Dahl’s hypothesis that a saluretic substance may be responsible for a sustained run in arterial pressure Its possible role in essential hypertension. Kidney Int 1980; 18: 1-9
LOW-DOSE DOXAPRAM FOR APNOEA OF PREMATURITY
SIR,-Doxapram has been proposed for the treatment of idiopathic apnoea in premature babies when methylxanthines have failed. Usually the two drugs have been given together.l-3 Since small doses of doxapram have a selective action on ventilatory drive and since larger doses can cause central-nervous-system toxicity (eg,
convulsions)4,5 we decided to try doses lower than those previously
’p<0
os, tp
1 (pained t tests).
proposed. In a pilot study doxapram was given intravenously at a dose of 0. 25 mg kg-1h-1(6 mg/kg daily) instead of 2 - 5 mg kg-11 h- 1. All infants (see table) had at least six daily episodes of recurrent idiopathic apnoea lasting 15 s or more with a heart rate below 80/min despite treatment with caffeine (10 mg/kg loading dose and