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(Circulation. 1997;96:1859-1862.)
© 1997 American Heart Association, Inc.
Articles |
Sodium Restriction Shifts Circadian Rhythm of Blood Pressure From Nondipper to Dipper in Essential Hypertension
From the Division of Nephrology, National Cardiovascular Center, Osaka, Japan.
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Abstract |
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Background Sodium restriction has been widely used for treatment of hypertension and renal diseases. Whether sodium restriction can transform the circadian rhythm of blood pressure from nondipper to dipper is examined.
Methods and Results Patients (n=42) with essential
hypertension were maintained on a high-sodium diet (12 to 15 g of
NaCl per day) and a low-sodium diet (1 to 3 g/d) for 1 week each. On
the last day of each diet, blood pressures were measured noninvasively
every hour for 24 hours with an automatic oscillometric device.
Twenty-one patients were classified as non–sodium sensitive whereas 21
were classified as sodium sensitive on the basis of a 
10% change in
24-hour mean arterial pressure caused by sodium restriction. Nocturnal
blood pressure fall was significant in the non–sodium sensitive
subjects but not in sodium-sensitive subjects. There was a significant
interaction between sodium restriction and nocturnal fall in blood
pressure only in the sodium-sensitive subjects, indicating that the
degree of the nocturnal fall was affected by sodium restriction.
Furthermore, changes in the nocturnal fall induced by sodium
restriction had a positive relationship with sodium sensitivity
(r=.38, P<.02) and a negative relationship with
the nocturnal fall before sodium restriction (r=-.75,
P<.0001).
Conclusions These findings show the difference in nocturnal fall in blood pressure between the non–sodium sensitive and sodium-sensitive types of essential hypertension. The diminished nocturnal fall, recognized in the sodium-sensitive type, is restored by sodium restriction, indicating that the circadian rhythm of blood pressure shifted from a nondipper to a dipper pattern. On the other hand, the nocturnal fall is not affected by sodium restriction in the non–sodium sensitive type, and the circadian rhythm remains of the dipper variety.
Key Words: circadian rhythm • blood pressure • sodium • kidney
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In patients with essential hypertension, it has been postulated that the lack of a nocturnal fall in BP (nondipper) is associated with more serious end-organ damage, such as left ventricular hypertrophy, microalbuminuria, and cerebrovascular disease,1 2 3 4 than is found in dippers, whose BP falls during the night. Recently, we5 found that BP failed to fall during the night in patients with the SS type of essential hypertension, especially during a high-sodium diet. In addition, we also showed that the nocturnal fall in BP was less during high sodium intake with higher sodium sensitivity, whereas during low sodium intake, it was independent of sodium sensitivity.5 These findings suggested that sodium restriction might restore the nocturnal fall in BP. In the present study, therefore, we attempted to clarify whether the nocturnal fall and circadian BP rhythm were affected by the amount of sodium intake.
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Methods |
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Forty-two Japanese patients with essential hypertension (27 men and 15 women; age, 27 to 68 years [mean, 49±11 years]), each of whom had given their informed consent, were studied in the National Cardiovascular Center Hospital in Osaka, Japan. Antihypertensive drugs were discontinued at least 2 weeks before hospitalization until completion of the study periods. After the initial 1- to 2-week hospitalization, during which BP was stabilized, serum creatinine concentration was measured and patients were subjected to the following study protocol, which lasted another 2 weeks with patients hospitalized, as previously reported.5
Patients were maintained on a high-sodium diet containing 12 to 15 g of NaCl per day (stage I) and a low-sodium diet containing 1 to 3 g of NaCl per day (stage II) for 1 week each, in randomized order. On the last day of each stage, BP was measured noninvasively every hour for 24 hours with an automatic oscillometric device (model BP8800NC, Nippon Colin). MAP was calculated as diastolic BP plus one third of pulse BP. The daytime BP was calculated as the average of the 17 readings taken between 6 am and 10 pm, and nighttime BP was calculated as the average of the remaining 7 readings. The nocturnal fall in MAP was calculated as the difference between daytime and nighttime MAP.
UNaV was measured on the last 3 days of each stage of the study. Patients whose average 24-hour MAP was lowered >10% by sodium restriction were classified as SS; the remaining patients were classified as NSS.6 7 The sodium-sensitivity index was calculated as the ratio of the change in 24-hour MAP over the change in UNaV from stage I to stage II by sodium restriction5 7 8 9 10 11 12 and represents to what degree MAP is affected in the steady state by each millimolar alteration in daily sodium intake.7 The change in nocturnal MAP fall induced by sodium restriction was calculated as the difference between stages II and I.
Results are expressed as mean±SD. Determinations of the significance
of differences in the sodium-sensitivity index, age, sex distribution,
body mass index, and UNaV were made by Student's
t test for paired and unpaired samples and by
2 test as appropriate. The significance of the
effects of sodium restriction and nocturnal fall on BP, as well as
their interaction, was tested by a two-way ANOVA and ANCOVA with
repeated measures. The presence of an alternating action by this
analysis was considered as the evidence of an interaction
between sodium restriction and nocturnal fall. The significance of
differences in BP and heart rate between NSS and SS subjects was also
tested by two-way ANOVA. The correlation coefficient was obtained by
the least-squares method .
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Results |
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Among 42 patients with essential hypertension, 21 were classified as NSS and 21 as SS. The sodium-sensitivity index was 0.0075±0.0580 and 0.090±0.026 mm Hg · mmol-1 · d-1 (P<.0001) in NSS and SS subjects, respectively. No significant differences were detected in age (48±12 versus 51±11 years), sex distribution (male/female: 15/6 versus 12/9), body mass index (24.1±4.0 versus 25.1±4.4 kg/m2), or serum creatinine concentration (82±14 versus 85±14 µmol/L [0.9±0.2 versus 1.0±0.2 mg/dL]) between NSS and SS subjects, respectively. UNaV was 194±40 and 201±52 mmol/d during the high-sodium diet period, which was reduced to 32±13 and 28±14 mmol/d during the low-sodium diet period in NSS and SS types, respectively.
The average values of systolic BP, diastolic BP,
MAP, and heart rate during daytime and nighttime before and after
sodium restriction are shown in the
Table
. During the high-sodium diet, BPs
in the SS subjects were all higher than those in the NSS subjects.
During the low-sodium diet, on the other hand, BPs in the SS subjects
were all lower than in the NSS subjects. Sodium restriction
significantly lowered only systolic BP and MAP in NSS subjects,
whereas it lowered systolic BP, diastolic BP, and
MAP in SS subjects. The nocturnal falls of all BPs from daytime to
nighttime were significant in NSS subjects, but none were significant
in SS subjects. In SS subjects only, there was a significant
interaction between sodium restriction and nocturnal fall in MAP and in
diastolic BP, indicating that the degree of nocturnal MAP
fall was affected by sodium restriction. In both types of essential
hypertension, the heart rate was significantly reduced from daytime to
nighttime. Sodium restriction increased the heart rate in NSS subjects,
whereas was unchanged in SS subjects.
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Fig 1 compares the effects of sodium
restriction and nocturnal MAP fall, as well as their interaction,
between the NSS and SS types of essential hypertension. In NSS
subjects, nocturnal MAP fall was not affected by sodium restriction. In
SS subjects, on the other hand, nocturnal MAP fall was significantly
enhanced by sodium restriction, because there was an interaction
(alternating action; P<.05) between the effects on MAP of
sodium restriction and nocturnal fall.
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and 
, MAP
values during high- and low-sodium diets, respectively. Error bars
indicate either the upper or the lower half of the 95% CI.
Furthermore, as shown in Fig 2, changes
in the nocturnal MAP fall induced by sodium restriction had a positive
relationship with the sodium-sensitivity index (r=.38,
P<.02) and a negative relationship with the nocturnal MAP
fall during the high-sodium diet (r=-.75,
P<.0001). Taken together, these findings showed the
nocturnal MAP fall to be different between the two types of essential
hypertension. The diminished nocturnal fall, recognized in the SS type
of essential hypertension, was restored by sodium restriction,
indicating that the circadian rhythm of blood pressure shifted from a
nondipper to a dipper pattern. On the other hand, the nocturnal fall
was not affected by sodium restriction in the NSS type of hypertension,
and the circadian rhythm remained in a dipper pattern.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Our recent study5 showed that MAP failed to fall during the night in patients with the SS type of essential hypertension, who therefore manifested as nondippers. In addition, we also showed previously that the nocturnal MAP fall was less during a high-sodium diet with higher sodium sensitivity of BP, whereas during a low-sodium diet, it was independent of sodium sensitivity.5 The present study, which is an extension of our previous one,5 clearly showed different patterns of the nocturnal fall in NSS and SS subjects. The diminished nocturnal fall was restored by sodium restriction in SS subjects, demonstrating that the circadian rhythm of BP was transformed from a nondipper to a dipper pattern. On the other hand, the nocturnal fall was not affected by sodium restriction in NSS subjects, and the circadian rhythm remained in a dipper pattern. This statement can be further generalized to say that as the nocturnal fall is diminished, sodium restriction restores the nocturnal fall to a greater extent. In fact, there was a strong negative relationship between the nocturnal MAP fall before sodium restriction and the change in nocturnal MAP fall induced by sodium restriction.
Sodium restriction has been considered one of the most important lifestyle modifications as well as therapeutic strategies in the field of both hypertension and renal diseases. We have postulated on a theoretical basis that in the SS type of hypertension, glomerular capillary hydraulic pressure is elevated; in all animal models examined whose BP is expected to be sensitive to a change in sodium intake, glomerular capillary pressure indeed proved elevated.6 7 As renal function deteriorates and the number of functioning nephrons is reduced, glomerular capillary pressure is elevated in the remaining nephrons.13 14 In turn, this glomerular hypertension accelerates the speed of the long-term loss of function, resulting in glomerular sclerosis and eventual end-stage renal failure.15 16 17 18 In this regard, all animal models characterized by high sodium sensitivity show more profound renal injury and eventually progress to renal failure.6 7 Recently, we11 quantitatively estimated that glomerular capillary pressure was elevated in patients with the SS type of essential hypertension. In addition, we showed that renal function reserve in response to chronic protein load was lost in this type of hypertension,11 consistent with elevated glomerular capillary pressure. It has been reported that glomerular capillary pressure was elevated in black patients with SS hypertension19 and that the urinary albumin excretion rate, which may be a marker of glomerular capillary hypertension,20 21 is greater in the SS type of essential hypertension than in the NSS type.21 22 On the other hand, it is well established in advanced chronic renal failure that BP increases and becomes SS.8 Sodium sensitivity is enhanced even when the glomerular filtration rate remains normal in patients with chronic glomerulonephritis,23 and it becomes much greater as the glomerular filtration rate declines8 23 and as BP is elevated.24 Similarly, an animal model of glomerulonephritis indicates that even when the glomerular filtration rate remains normal, the ultrafiltration coefficient is reduced, with glomerular capillary pressure rising in compensation.25 26 27 28 As stated above, the present study showed that in patients with the SS type of essential hypertension, BP failed to fall during the night, and they manifested as nondippers.5 This is consistent with reports that black Americans, who are very SS, have a minimal nocturnal decline in BP29 and that the urinary albumin excretion, which is increased in the SS type of essential hypertension,21 is greater in nondippers than in dippers.30 On the other hand, it is well known that in patients with renal dysfunction, the nocturnal fall is lost, and they manifest as nondippers.31 32 33 It is also interesting to note a recent report34 that nondippers with renal dysfunction progress more rapidly to renal failure than dippers. Thus, diminished nocturnal fall (that is, nocturnal hypertension) in SS patients may correlate with increased glomerular capillary pressure (that is, glomerular hypertension). High sodium sensitivity may be a marker of a greater risk of renal and cardiovascular complications, because nondippers showed strong evidence of more organ damage, such as left ventricular hypertrophy and cerebrovascular accidents, than dippers.1 2 3 4 Sodium restriction may relieve the renal and cardiovascular risks in several different ways: systemic BP reduction, normalization of circadian BP rhythm, lowering of glomerular capillary pressure, and reduction of urinary protein excretion.
The present data also imply that diminished renal sodium excretory capability, recognized as a reduced ultrafiltration coefficient in the SS type of essential hypertension,11 determines the circadian rhythm of BP. When sodium intake is high, the defect in sodium excretory capability becomes evident, elevating MAP during the night (that is, nocturnal hypertension or nondipper) to compensate for diminished natriuresis during the day and causing enhanced pressure natriuresis during the night.35 When sodium intake is low, on the other hand, the defect remains latent, allowing MAP to be lowered during the night (dipper). These speculations, together with the above links among sodium sensitivity, glomerular capillary hypertension, proteinuria, renal dysfunction, and nondipper status, suggest that the circadian rhythm of BP is determined at least in part by the kidneys.
In conclusion, the present study demonstrated for the first time that in patients with the SS type of essential hypertension, diminished nocturnal BP decline was restored by sodium restriction, and the circadian rhythm of BP was shifted from nondipper to dipper. Sodium restriction may have an additional therapeutic advantage to reduce the risk for cardiovascular complications by transforming the above circadian rhythm of BP.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by research grants for cardiovascular diseases (C-1994-6 and C-1995-3) and for progressive renal disease from grants for specially selected diseases by the Ministry of Health and Welfare Research Project as well as for scientific research expenses for Health and Welfare programs and funds for comprehensive research on long-term chronic disease (renal failure), all from the Ministry of Health and Welfare of Japan. The authors thank Keiko Tanegashima for her excellent secretarial work.
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Footnotes |
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Reprint requests to Takashi Uzu, MD, Division of Nephrology, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565, Japan.
Received March 3, 1997; revision received April 30, 1997; accepted May 2, 1997.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. O'Brien E, Sheridan J, O'Malley K. Dippers and non-dippers. Lancet. 1988;2:397.[Medline] [Order article via Infotrieve]
2.
Verdecchia P, Schillaci G, Guerrieri M, Gatteschi C,
Benemio G, Boldrini F, Porcellati C. Circadian blood pressure
changes and left ventricular hypertrophy in
essential hypertension. Circulation. 1990;81:528-536.
3.
Shimada K, Kawamoto A, Matsubayashi K, Ozawa T.
Silent cerebrovascular disease in the elderly: correlation with
ambulatory pressure. Hypertension. 1990;16:692-699.
4.
Verdecchia P, Porcellati C, Schillaci G, Borgioni C,
Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A,
Santucci C, Reboldi G. Ambulatory blood pressure: an independent
predictor of prognosis in essential hypertension.
Hypertension. 1994;24:793-801.
5.
Uzu T, Kazembe FS, Ishikawa K, Nakamura S, Inenaga T,
Kimura G. High sodium sensitivity implicates nocturnal
hypertension in essential hypertension.
Hypertension. 1996;28:139-142.
6. Kimura G, Brenner BM. A method for distinguishing salt-sensitive from non-salt-sensitive forms of human and experimental hypertension. Curr Opin Nephrol Hypertens. 1993;2:341-349.[Medline] [Order article via Infotrieve]
7. Kimura G, Brenner BM. The renal basis for salt sensitivity in hypertension. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis and Management. New York, NY: Raven Press; 1995:1569-1588.
8.
Koomans HA, Roos JC, Boer P, Geyskes GG, Dorhout Mees
EJ. Salt sensitivity of blood pressure in chronic renal failure:
evidence for renal control of body fluid distribution in man.
Hypertension. 1982;4:190-197.
9.
Kimura G, Saito F, Kojima S, Yoshimi H, Abe H, Kawano
Y, Yoshida K, Ashida T, Kawamura M, Kuramochi M, Ito K, Omae T.
Renal function curve in patients with secondary forms of
hypertension. Hypertension. 1987;10:11-15.
10.
Saito F, Kimura G. Antihypertensive mechanism of
diuretics based on pressure-natriuresis relationship.
Hypertension. 1996;27:914-918.
11. Sanai T, Kimura G. Renal function reserve and sodium sensitivity in essential hypertension. J Lab Clin Med. 1996;128:89-97.[Medline] [Order article via Infotrieve]
12. Kimura G, Uzu T, Nakamura S, Inenaga T, Fujii T. High sodium sensitivity and glomerular hypertension/hyperfiltration in primary aldosteronism. J Hypertens. 1996;14:1463-1468.[Medline] [Order article via Infotrieve]
13.
Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA,
Brenner BM. Hyperfiltration in remnant nephrons: a potentially
adverse response to renal ablation. Am J
Physiol. 1981;241:F85-F93.
14. Pelayo JC, Quan AG. Pathophysiology of glomerular hemodynamic adaptations to nephron loss. Semin Nephrol. 1989;9:10-13.[Medline] [Order article via Infotrieve]
15. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982;307:652-659.[Medline] [Order article via Infotrieve]
16. Brenner BM. Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int. 1983;23:647-655.[Medline] [Order article via Infotrieve]
17. Brenner BM, Cohen RA, Milford EL. In renal transplantation, one size may not fit all. J Am Soc Nephrol. 1992;3:162-169.[Medline] [Order article via Infotrieve]
18. Brenner BM, Chertow GM. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis. 1994;23:171-175.[Medline] [Order article via Infotrieve]
19.
Campese VM, Parise M, Karubian F, Bigazzi R.
Abnormal renal hemodynamics in black salt-sensitive
patients with hypertension. Hypertension. 1991;18:805-812.
20.
Yoshioka T, Rennke HG, Salant DJ, Deen WM, Ichikawa
I. Role of abnormally high transmural pressure in the
permselectivity defect of glomerular capillary wall: a
study in early passive Heymann nephritis. Circ Res. 1987;61:531-538.
21.
Bigazzi R, Bianchi S, Baldari D, Sgherri G, Baldari G,
Campese VM. Microalbuminuria in salt-sensitive
patients: a marker for renal and cardiovascular risk
factors. Hypertension. 1994;23:195-199.
22.
Weir MR, Dengel DR, Behrens MT, Goldberg AP.
Salt-induced increases in systolic blood pressure affect renal
hemodynamics and proteinuria.
Hypertension. 1995;25:1339-1344.
23. Cianciaruso B, Bellizzi V, Minutolo R, Colucci G, Bisesti V, Russo D, Conte G, De Nicola L. Renal adaptation to dietary sodium restriction in moderate renal failure resulting from chronic glomerular disease. J Am Soc Nephrol. 1996;7:306-313.[Abstract]
24. Kumagai H, Onoyama K, Fujishima M. Effects of salt restriction on blood volume, hemodynamics and humoral factors in patients with chronic glomerulonephritis. Am J Hypertens. 1989;2:669-674.[Medline] [Order article via Infotrieve]
25. Allison MEM, Wilson CB, Gottschalk CW. Pathophysiology of experimental glomerulonephritis in rats. J Clin Invest. 1974;53:1402-1423.
26. Maddox DA, Bennett CM, Deen WM, Glassock RJ, Knutson D, Daugharty TM, Brenner BM. Determinants of glomerular filtration in experimental glomerulonephritis in the rat. J Clin Invest. 1975;55:305-318.
27. Blantz RC, Wilson CB. Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat. J Clin Invest. 1976;58:899-911.
28. Gabbai FB, Gushwa LC, Wilson CB, Blantz RC. An evaluation of the development of experimental membranous nephropathy. Kidney Int. 1987;31:1267-1278.[Medline] [Order article via Infotrieve]
29.
Harshfield GA, Alpert BS, Willey ES, Somes GW, Murphy
JK, Dupaul LM. Race and gender influence ambulatory blood
pressure patterns of adolescents. Hypertension. 1989;14:598-603.
30. Bianchi S, Bigazzi R, Baldari G, Sgherri G, Campese VM. Diurnal variations of blood pressure and microalbuminuria in essential hypertension. Am J Hypertens. 1994;7:23-29.[Medline] [Order article via Infotrieve]
31. Rosansky SJ, Johnson KL, Hutchinson C, Erdel S. Blood pressure changes during daytime sleep and comparison of daytime and nighttime sleep-related blood pressure changes in patients with chronic renal failure. J Am Soc Nephrol. 1993;4:1172-1177.[Abstract]
32. Baumgart P, Walger P, Gemen S, von Eiff M, Raidt H, Rahn KH. Blood pressure elevation during the night in chronic renal failure, hemodialysis and after renal transplantation. Nephron. 1991;57:293-298.[Medline] [Order article via Infotrieve]
33. Portaluppi F, Montanari L, Massari M, Di Chiara V, Capanna M. Loss of nocturnal decline of blood pressure in hypertension due to chronic renal failure. Am J Hypertens. 1991;4:20-26.[Medline] [Order article via Infotrieve]
34. Timio M, Venanzi S, Lolli S, Lippi G, Verdura C, Monarca C, Guerrini E. "Non-dipper' hypertensive patients and progressive renal insufficiency: a 3-year longitudinal study. Clin Nephrol. 1995;43:382-387.[Medline] [Order article via Infotrieve]
35. Staessen JA, Birkenhager W, Bulpitt CJ, Fagard R, Fletcher AE, Lijnen P, Thijs L, Amery A. The relationship between blood pressure and sodium and potassium excretion during the day and at night. J Hypertens. 1993;11:443-447.[Medline] [Order article via Infotrieve]
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