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Published ahead of print on January 10, 2007
Clin J Am Soc Nephrol 2: 304-312, 2007
© 2007 American Society of Nephrology
doi: 10.2215/CJN.03401006
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Hypertension

Ethnic Differences in Urine Concentration: Possible Relationship to Blood Pressure

Lise Bankir*,{dagger}, Julie Perucca*,{dagger}, and Myron H. Weinberger{ddagger}

* INSERM, Unité 652, and {dagger} Université Paris Descartes, Centre des Cordeliers, Paris, France; and {ddagger} Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

Address correspondence to: Dr. Lise Bankir, INSERM Unité 652, 17 Rue du Fer à Moulin, 75005 Paris, France. Phone: +33-1-45-87-61-21; Fax: +33-1-45-35-66-29; E-mail: bankir{at}fer-a-moulin.inserm.fr


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 Disclosures
 References
 
The mechanisms that account for the susceptibility of black individuals to hypertension and their reduced ability to excrete sodium are poorly understood. Vasopressin administration has been shown in healthy humans to delay sodium excretion along with its antidiuretic action. Black individuals have been reported to have higher vasopressin levels than white individuals. Therefore, this study investigated retrospectively 24-h urine volume (V) and urine concentration index (urine-to-plasma ratio of creatinine concentration), as well as their possible relationships with BP, in a cohort of 141 healthy young black and white individuals (18 to 40 y). Black individuals were found to have a significantly lower V and higher urine concentration than white individuals, especially during daytime. In addition, they exhibited a blunted nocturnal fall in fluid and electrolyte excretion and a higher pulse pressure than white individuals. Higher urine concentration and lower V were associated significantly with higher PP (but not with systolic or diastolic BP) in men. These relations remained significant after adjustment for age, body mass index, and sodium and potassium excretion. These results suggest that an enhanced tendency to concentrate urine may delay the excretion of the daily ingested fluid and sodium and may increase pulse pressure in young normotensive individuals. The higher urine concentration that is observed in black individuals (which could represent an adaptation to better water conservation) may participate in their enhanced susceptibility to hypertension. If these results are confirmed in further studies, then vasopressin V2 receptor antagonists might offer a novel antihypertensive strategy, especially in the black population.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 Disclosures
 References
 
High BP is known to be more common in individuals of black ethnic background than in white individuals, but the mechanisms involved are poorly understood. Black individuals on average excrete sodium less efficiently than do white individuals (1,2). Several studies suggest that a reduced capacity of the kidney to excrete sodium participates in sodium and fluid retention (3,4), and this renal dysfunction is thought to play a role in the greater prevalence of salt-sensitive hypertension in black individuals (5,6).

The possible involvement of vasopressin in hypertension and cardiovascular disease has been suspected for a long time because of the vasoconstrictive properties that are mediated by V1a receptors expressed in vascular smooth muscle cells. However, although vasopressin was found in some studies to be elevated in hypertensive patients (7,8) and animal models (9,10), its contribution to hypertension has remained inconclusive. Moreover, the administration of a highly selective nonpeptide V1a receptor antagonist did not lower BP in hypertensive patients (11). Less attention has been given to the possible contribution of vasopressin to high BP by its antidiuretic effects that are mediated by the renal V2 receptors, despite that vasopressin has been known for two decades to stimulate sodium reabsorption in the cortical and outer medullary collecting duct (see review in reference [12]).

Studies in healthy volunteers suggest that an increased stimulation of V2 receptors reduces the excretion of endogenous sodium and the ability of the kidney to excrete an exogenous hypertonic sodium load (13,14). This antinatriuretic effect of vasopressin should improve water conservation at the cost of a less efficient sodium excretion, at least in the short term, as proposed previously (13,15). Under chronic excessive V2 receptor stimulation, sodium and water excretion could return to normal through an increase in BP, as observed in rats (16). In humans, excessive sodium reabsorption in the collecting duct, as a result of gain-of-function mutations in the epithelial sodium channel (ENaC), is responsible for Liddle’s syndrome, a severe form of hypertension (17). Thus, that vasopressin and/or the associated reduction in urine flow rate increases sodium reabsorption in the collecting duct in vitro and delays sodium excretion in vivo provides some support for the hypothesis that an excessive influence of vasopressin on the kidney and a low urine flow rate could participate in salt-sensitive hypertension. In addition, recent studies have drawn attention not only to 24-h urine volume but also to the day–night pattern of water and sodium excretion in relation to BP control (18–21).

In several studies, black individuals were reported to have higher vasopressin levels than white individuals (22–24), but to our knowledge, neither the causes of this difference nor its possible consequences on urine volume and concentration has been evaluated. This prompted us to reanalyze data from a study that was performed earlier in a large group of American black and white individuals who provided 24-h urine, separated into day and night fractions. This allowed us to compare urine volume and concentration as well as the circadian pattern of water and sodium excretion in the two ethnic groups and their relationships with BP.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 Disclosures
 References
 
The data were obtained in healthy volunteers and hypertensive patients who participated in studies that addressed hypertension and salt sensitivity of BP (3,5). The studies were conducted at the Indiana University Research Center and were approved by the Indiana University Medical Center Human Use Committee. All participants gave informed consent. This cohort included 347 white and black individuals of both genders. In the first 24 h after admission, the participants received a regular hospital diet that contained 150 mEq of sodium and 70 mEq of potassium. Ad libitum water intake was provided. No smoking, alcohol consumption, or exercise was permitted during the study. All measurements were stored in an electronic database, which was converted to an Excel file for our analyses. Here, a subset of 141 individuals was selected from the initial cohort on the basis of the following inclusion criteria: Age 18 to 40 yr and body mass index (BMI) 18 to 39 kg/m2. We excluded individuals with creatinine clearance <65 ml/min per 1.73 m2 or with differences between day and night creatinine excretion rates >50% (suggesting incomplete urine collection in one of the periods). All but five of the 141 individuals who met these criteria and subsequently were considered in this study were normotensive (i.e., systolic BP [SBP] <140 mmHg or diastolic BP [DBP] <90 mmHg). None of the five hypertensive individuals (one white woman and one black woman and two white men and one black man) were taking antihypertensive medication.

As reported in the initial publications, all individuals were studied under basal conditions for 24 h (before they underwent protocols that were intended to test their sodium sensitivity) (3,5). The data analyzed here concern only this basal day during which urine was collected into two separate fractions: From 6 a.m. to 10 p.m. (day) and from 10 p.m. to 6 a.m. (night). A blood sample was taken at 8 a.m. In all serum and urine samples, creatinine, sodium, and potassium were measured, and urine flow rate (V), sodium and potassium excretion rates, and creatinine clearance were calculated. Specially trained nurses using mercury manometers measured the BP at 8 a.m., 12 p.m., 5 p.m., and 9 p.m. The fifth Korotkoff component, or point of sound disappearance, was accepted as the diastolic pressure. Each value was the mean of the last two of three successive readings in the sitting position.

Urine osmolality (Uosm) was not measured. Therefore, for these analyses, we used an indirect method to estimate urine concentration. Because water but not creatinine is reabsorbed progressively along the successive nephron segments, creatinine concentration rises proportionally in the tubular fluid and collecting duct urine above its plasma value. Therefore, the ratio of urine to serum creatinine concentrations provides an index of urine concentration (urine concentration index [UCI]). We observed previously that UCI is correlated linearly and positively with Uosm (19,25). This allowed us to estimate Uosm from the UCI values. Effective free water clearance (electrolyte-dependent free water clearance [eFWC]) was calculated according to the classic formula as V x [1 – (UNa + UK)/SNa], where UNa or UK, and SNa are the concentrations of sodium or potassium in urine (U) or serum (S). With regard to BP, the average of the 12 p.m. and 5 p.m. measurements was used in these analyses to represent the BP that prevailed during the daytime period of urine collection. Pulse pressure (PP) was calculated (SBP – DBP). SBP, DBP, and PP at the two time points were averaged in each individual.

Ethnic differences were evaluated by t test. When gender was considered in addition to race, two-way ANOVA was used, followed by Fisher post hoc test. Linear regression and correlation coefficients were used to evaluate the relationships between pressure and urine data. Additional correlations of PP with urine volume and UCI were tested by multiple linear regression with adjustment for age, BMI, and 24-h sodium and potassium excretions using SPSS software (SPSS, Chicago, IL). The percentages of black and white individuals with positive eFWC were compared by {chi}2 test. P < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 Disclosures
 References
 
Demographics for the 141 individuals are presented in Table 1. Black and white men and women did not differ with regard to age, but black individuals had higher BMI than white individuals. All four groups had similar serum sodium and sodium excretion rates. As has been reported previously (3,26,27), black individuals had a significantly lower serum potassium and potassium excretion rate than white individuals. Serum creatinine and creatinine excretion rate were higher in men than in women and in black individuals than in white individuals, as already known.


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  		Table 1. Demographics and 24-h urine dataa

 
Trend to Concentrate Urine in Black and White Individuals
As shown in Figure 1, A and B, and Table 1, 24-h urine volume (whether in absolute values or factored by 1.73 m2) was significantly lower and UCI higher in black than in white individuals. In contrast, creatinine clearance did not differ between the two ethnic groups (Figure 1C). Sodium concentration in the urine also was significantly higher in black than in white individuals in both genders (Table 1). Estimated Uosm in men averaged 544 and 693 mOsm/kg H2O in white and black individuals, respectively, and in women averages 421 and 574 mOsm/kg H2O, respectively. Thus, black individuals of both genders concentrated urine by approximately 150 mOsm/kg H2O more than white individuals. A significant gender difference also was revealed with women having Uosm approximately 120 mOsm/kg H2O less than men and urine volumes approximately 200 ml higher in both ethnic groups (Table 1), although women usually eat less and excrete fewer solutes than men. It also is interesting to note the wide interindividual variability that was observed in urine volume and UCI (Figure 1D). The 24-h UCI varied from 50 to 290 in men and from 50 to 240 in women, and the urine volume ranged from 500 to 2460 ml/d in men and from 600 to 3600 ml/d in women, both variables spanning a five- to six-fold range. These interindividual differences probably are paralleled by a similar diversity in the thirst/fluid intake/vasopressin axis, the intensity and thresholds of which are under genetic influence, at least in part (28).


Figure 1
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  		Figure 1. (A through C). Twenty-four-hour urine volume, urine concentration index (UCI), and creatinine clearance in black and white men and women. Data are means ± SEM. P values correspond to differences between black and white individuals in each gender group. (D) Individual values for UCI in the four subgroups. In B and D, the corresponding urine osmolality (Uosm) is shown.

 
Day–Night Pattern of Water and Solute Excretion in Black and White Individuals
Separate urine collection during day and night periods allowed us to compare the circadian pattern of water and solute excretion in black and white individuals. During the day, urine flow rate was 30% lower in black than in white men (P = 0.027; Figure 2) and 22% lower in black than in white women (P = 0.106, NS). Conversely, UCI during the day was higher in black than in white individuals by 24% in men (P = 0.01; Figure 2) and by 36% in women (P = 0.007). In all groups, urine flow rate fell and UCI increased at night. However, these day–night differences were smaller in black than in white individuals of both genders (Figure 2 and Table 2). At night, urine flow rate and UCI did not differ between black and white men (Figure 2) or women (data not shown). During daytime, the eFWC was almost three times lower in black than in white individuals (–14.2 ± 3.2 versus –5.1 ± 4.0 ml/h), although this difference did not reach statistical significance. Among black individuals, only 12% had a positive eFWC versus 33% in white individuals (P < 0.02). These differences were absent or largely blunted at night. It is interesting that a significant correlation was observed between the UCI and the BMI in men during the day (UCI = 3.03 BMI + 68; r = 0.233, P < 0.05) but not during the night. A similar trend was observed in women. A similar correlation was reported previously in men with mild essential hypertension (19).


Figure 2
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  		Figure 2. Urine flow rate and UCI, creatinine clearance, and excretion of the different solutes during day and night separately, in black and white men. Data are means ± SEM of 26 black (•) and 64 white men ({circ}). When SEM are not visible, they are smaller than the symbols. P values correspond to differences between black and white men for each period.

 

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  		Table 2. Day/night ratios for urine dataa

 
Sodium excretion rate was higher during daytime than during nighttime (Figure 2), with day/night ratio that did not differ significantly between ethnic groups in either gender (Table 2). Potassium showed larger differences in excretion rates between day and night than that observed for water or sodium, especially in men (Figure 2 and Table 2). The lower 24-h excretion rate of potassium in black individuals, previously documented in several studies, seems to be confined to daytime. In contrast, the higher creatinine excretion in black individuals was apparent mostly at nighttime. Creatinine clearance in black men was approximately 9 ml/min lower during the day and 12 ml/min higher during the night than in white men, although these differences did not reach statistical significance (Figure 2). Table 2 shows that the mean day/night ratios for the different variables were in every instance lower in black than in white individuals, revealing a blunted diurnal pattern of water and electrolyte excretion in the former. The day/night ratio for creatinine clearance in men was significantly lower in black than in whites individual, but this difference was not observed in women (Table 2). Thus, the usual nocturnal fall in GFR was blunted in black men (18 versus 39 ml/min in white men).

BP and Relationships between BP and Water and Solute Excretion
Table 1 shows the BP results in the four subgroups. SBP was 6 mmHg higher and DBP was 1 mmHg lower in black than in white men. These differences resulted in a PP 7 mmHg higher in black men than in white men (P = 0.002). SBP, DBP, and PP were similar in women of the two ethnic groups (Table 1). To evaluate the possible relationships between BP and an individual’s trend to concentrate urine, we examined correlations between SBP, DBP, or PP and the 24-h urine flow rate or the UCI. Possible confounding factors such as age, obesity, and the level of sodium or potassium intake (as estimated from the corresponding excretion) also were evaluated. Correlation coefficients and their statistical significance for men are shown in Table 3. In men, significant positive correlations were found between SBP and DBP with age and BMI and negative correlations between SBP and 24-h potassium excretion. PP was correlated negatively with 24-h sodium excretion and urine volume and correlated positively with UCI (Table 3). In women (data not shown), none of the correlations was significant except for SBP and DBP with age (r = 0.371 and 0.342, respectively, P < 0.01 for each). The correlation coefficients for other linear regressions in women all were <0.150.


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  		Table 3. Correlation coefficients and statistical significance of linear regressions between SBP, DBP, or PP and several other variables in white and black mena

 
It is interesting to note that SBP and DBP were not correlated significantly with 24-h urine volume or UCI but that PP, their difference, was correlated positively with UCI and negatively with urine volume in men (Table 3 and Figure 3). Multiple linear regression confirmed that these relations were independent of the mean BP. The correlation coefficients and the level of significance were higher for PP with urine volume and UCI than with sodium or potassium excretion, suggesting a stronger relationship of PP with the concentrating activity of the kidney than with the sodium or potassium intake (Table 3). The relationship between PP and urine volume in men was significant regardless of whether three outliers with unusually high urine volume were included or excluded (Figure 3). Thus, PP tended to be higher in men who produce smaller amounts of urine that is of higher concentration. This trend was absent in women (Figure 3) and was not seen in men when the early morning BP measurements, taken after an overnight fast, were considered (data not shown).


Figure 3
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  		Figure 3. Relationship between pulse pressure (PP) and 24-h urine volume (V) or UCI in men (n = 86) and women (n = 50). •, Black individuals in each gender group; {circ}, white individuals in each gender group. For men, separate regression lines are shown for black (thick line) and white individuals (thin line), but the correlation coefficients (r) and statistical significance concern all men together. Three white men with unusually high 24-h urine volume were excluded from the regression analysis.

 
When white and black men were analyzed separately (Figure 3), black men exhibited a 5-mmHg higher PP than white men for any given urine volume or UCI, but the slopes of the regression lines were almost identical (i.e., the two regression lines are parallel), suggesting that the relationships of PP with urine volume or urine concentration are not affected by ethnicity. Noteworthy, these relationships seem to be stronger in black than in white individuals (although they reach significance only in the latter) because the correlation coefficients are higher in black (0.333 and 0.351 for PP with urine volume and UCI, respectively) than in white individuals (0.265 and 0.260, respectively; Table 3). The small number of black men prevented the correlations from reaching statistical significance, but the 24 black men probably contribute as much as or even more than the 64 white men to the significance that was found in the 90 men as a whole (Table 3).

To eliminate the possible influence of confounding factors, we performed a multiple regression analysis to evaluate the relationships of PP with 24-h urine volume or with UCI in all men (n = 90) with adjustment for age, BMI, and 24-h sodium and potassium excretion. Both relationships were significant (P = 0.028 and 0.011, respectively), with correlation coefficients of 0.337 and 0.362 for PP versus urine volume and UCI, respectively. These coefficient are as high as those found with the simple linear regression (Table 3). Thus, in the men of this study, the tendency for PP to rise with increasing urine concentration and to decrease with increasing urine volume seems to be independent of age, BMI, and sodium or potassium intake.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 Disclosures
 References
 
Our study reveals several new findings in a large group of healthy young adults. First, black individuals have a lower urine volume and a higher urine concentration than do white individuals and tend to have a blunted circadian pattern of water and solute excretion. Second, black men have a higher PP than do white men. Third, there are significant relationships between urine concentration and PP in men. To our knowledge, this is the first attempt to evaluate differences in urine volume and concentration as well as in circadian rhythm of water and solute excretion among different ethnic groups. It also is the first to look for possible relationships between the kidney’s tendency to concentrate urine and BP.

In both men and women, urine volume was approximately 20% lower and the UCI 20 to 30% higher in black than in white individuals. These differences are not due to differences in GFR, because creatinine clearance was similar in the two ethnic groups. Because Uosm is rarely measured in clinical investigations, especially in those that deal with BP regulation, we had to rely on an index of urine concentration, which has been shown to be well correlated with true Uosm in other studies. Tubular secretion of creatinine could increase UCI and lead to an overestimation of the kidney’s tendency to concentrate urine, but this secretion becomes significant only when plasma creatinine is elevated (29), as in chronic kidney disease or during infusion of exogenous creatinine. In any case, a significantly higher Uosm in black than in white individuals has already been observed (with direct Uosm measurements) in a cohort of normotensive young individuals who underwent an overnight urine collection (30) and in a study of normotensive and hypertensive age-matched black and white men (although the authors made no comment about this difference; see Table 2 in reference [8]).

Urinary sodium concentration, a variable that is independent of creatinine or urine volume measurements, also was higher in black than in white individuals, although serum sodium and total 24-h sodium excretion were the same. In the Intersalt study (31), which investigated the relationships between BP and sodium intake in 52 different centers around the world, the results of two centers in the United States were given separately for black and white individuals. Urine volume was lower in black than in white individuals (0.73 versus 1.14 L/d in Goodman and 1.03 versus 1.44 in Jackson), and urinary sodium concentration (recalculated from the 24-h excretion) was higher (131 versus 110 mmol/L, and 133 versus 93 mmol/L in the two cities, respectively), as in this study (compare with data shown in Table 1).

Retrospective studies cannot provide information about the factors that are responsible for the difference in urine concentration between black and white individuals. Some factors, however, can be proposed tentatively. That black individuals exhibit a lower urine flow rate than do white individuals suggests that they might have a less intense thirst and/or a higher vasopressin secretion. To our knowledge, no information is available regarding possible racial differences in thirst, but several independent studies have reported higher vasopressin levels in black than in white individuals (22–24). Associated changes in the thresholds for thirst and vasopressin secretion, as a result of a different set point of the hypothalamic "osmostat," could have provided a survival advantage with respect to the ability to conserve water in African populations. However, this adaptation could make them more susceptible to salt-induced increases in BP because a reduced urine flow rate was shown to reduce the ability to excrete sodium (13,14). This hypothesis is consistent with recently reported correlations, among 53 populations in diverse climates, between BP level and single-nucleotide polymorphisms of selected genes that are involved in heat adaptation (32). Higher thirst/vasopressin levels may counterbalance the lower activity of the renin-angiotensin-aldosterone system (RAAS) that is commonly observed in black individuals. Actually, in a population-based sample of 534 middle-aged individuals, an association between plasma vasopressin and BP was observed, especially in patients with low renin (7). In rats with equivalent food intake, an increase in plasma renin activity was observed when vasopressin levels were reduced chronically by a three-fold increase in fluid intake (33). Both the thirst/vasopressin system and the RAAS exert vasoconstrictive and sodium-retaining effects, but only vasopressin has a potent and rapid action on water conservation. Therefore, with stronger needs for a tighter control of fluid balance, the thirst/vasopressin system may have been favored whereas the RAAS was reduced.

Other factors also could account for a lower urine flow rate in black individuals, such as a reduced production of prostaglandins (34) or a lower activity of the kallikrein-kinin system (35), mediators that are known to blunt the antidiuretic effects of vasopressin. In addition, the lower potassium excretion in black individuals could contribute to their lower urine flow rate. Assuming that there is an upper limit to the capacity of the kidney to concentrate potassium in the urine, a higher potassium load will obligate a higher urine volume, as suggested recently (36).

Could a low 24-h urine volume and/or vasopressin effects on V2 receptors influence BP? Most previous studies addressed the possible contribution of vasopressin to hypertension through its vascular actions (7,22,37), but some recent studies drew attention to V2 receptor–mediated actions. Chronic infusion of dDAVP, a selective agonist of V2 receptors that is devoid of acute vasopressor effects, induced a significant increase in BP and aggravated Doca-salt hypertension in rats (16,38). Acute stimulation of V2 receptors by dDAVP was shown to reduce not only urine flow rate but also sodium excretion in healthy humans (13) and in the isolated erythrocyte-perfused rat kidney (39). This dDAVP-induced sodium retention is assumed to result from the direct stimulation of collecting duct ENaC by vasopressin (12). In addition, chronic alterations in V2 receptor stimulation were shown to influence the expression of the ß and {gamma} subunits of ENaC and amiloride-sensitive sodium transport in the collecting duct (15,16,40,41), whereas changes in sodium intake did not (41). It is interesting that salt-sensitive Sabra rats exhibit lower 24-h urine volume and higher urine osmolality than their salt-resistant counterparts, along with a higher hypothalamic expression and peripheral level of vasopressin (42). Altogether, these results suggest that the renal expression of ENaC is associated with the need to conserve water. As reviewed recently, ENaC may play a central role in the development of hypertension (43). In black hypertensive patients, ENaC inhibition by amiloride and aldosterone inhibition by spironolactone were shown to lower BP (44). Because vasopressin stimulates ENaC abundance and activity in the kidney, it may be proposed that the lower urine volume that is observed in black individuals may play a role in their difficulty to excrete sodium. If this were the case, then selective antagonism of V2 receptors also may be expected to improve sodium excretion and lower BP.

SBP and DBP did not differ significantly between black and white individuals in these young subjects. However, PP was higher in black than in white men. Although the relatively low number of female individuals is a limitation in this study, it may be proposed that the lack of an ethnic difference in PP in women is related to the fact that they concentrate urine much less than do men in this study, as in many others (25). Therefore, if low urine flow rate and high urine concentration contribute to retain sodium as explained above, then women may be at lesser risk for sodium retention than men. To our knowledge, a higher PP has not been documented previously in African Americans but was observed in black individuals living in Africa (45). Because the number of black men in our study was relatively small, this finding needs to be confirmed in a larger population. Several recent findings have emphasized the importance of PP as a significant determinant of cardiovascular morbidity and mortality (46–49). If a higher PP is confirmed in young normotensive black men in further studies, then black individuals may already be at greater risk for such adverse events before overt hypertension develops.

A positive correlation was found in men between PP and UCI and a negative correlation between PP and 24-h urine volume. These correlations were independent of age or BMI and of the 24-h sodium or potassium excretion rate. For a given osmolar load, a two-fold lower urine volume and a two-fold higher urine osmolality corresponded to an increase in PP by 6.6 mmHg (Figure 3). Although these correlations do not prove a causality link, a study in healthy individuals who received an acute hypertonic saline load suggests a direct link between vasopressin and PP in men (50). After the load, men exhibited a greater rise in plasma vasopressin and excreted a lesser fraction of the sodium load than did women. A significant rise in SBP and PP, which occurred only in men, suggested an upward shift in the pressure-natriuresis curve (50). In a chronic situation, a significant increase in PP was observed in response to a switch from low to high salt intake in young normotensive individuals (51). Therefore, an increase in PP might be an early event in salt-sensitive hypertension.

A few recent investigations focused attention on the circadian rhythm of water and/or sodium excretion in relation to BP (18–21,52). A greater tendency to concentrate urine, as seen in men compared with women and in black compared with white individuals, presumably lengthens the time spent by any ingested sodium in the body before being excreted, even if it does not compromise sodium balance on a 24-h basis. A low urine flow rate and/or sodium excretion rate during daytime seems to be compensated for at night at the price of a higher BP and thus of a lesser nocturnal dipping (53). A study in hypertensive individuals of the Seychelles (of African descent) suggests that the low sodium excretion during daytime is due to excessive reabsorption in the distal nephron (21). In this context, the blunted circadian pattern of water, sodium, and potassium excretion that was observed in black individuals in our study is consistent with the less intense nocturnal dipping of BP that was described previously in black individuals (54–56). That the correlation between PP and the 24-h urine volume or UCI was NS when the early morning PP was considered is in good agreement with this interpretation because sodium and fluid balance return to normal during the night. It is interesting that a disturbed circadian pattern of fluid and sodium excretion was described previously in moderately overweight individuals and in patients with diabetes and/or hypertension and was associated with a reduction in the nocturnal dipping of BP (18–20,52).


   Conclusion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
Disclosures
 References
 
This study emphasizes the potential relationships of urine flow rate and concentration that may bear on the control of BP and in the greater susceptibility of black individuals to hypertension. The results show that black men and women concentrate urine more than do white individuals and exhibit blunted day–night differences in water and electrolyte excretion. In addition, a significant positive correlation between PP and urine concentration was found in men as a whole. Therefore, a higher PP was associated with better water conservation. To our knowledge, no attention had been given in the past to possible ethnic differences in urine volume and osmolality. Therefore, this retrospective study opens interesting novel hypotheses, namely that a low urine volume in black individuals, as a result of different set points for the thirst/vasopressin axis and/or other factors that regulate water balance, may participate in their greater susceptibility to hypertension and cardiovascular disease. New prospective studies are needed to explore the thirst/vasopressin/urine concentration axis in parallel with the RAAS, paying attention also to possible associations between the circadian variations in BP and in water and solute excretion. If our results are confirmed, then newly developed nonpeptide vasopressin V2 receptor antagonists (57,58) might offer a novel antihypertensive strategy, especially in individuals in whom BP control is not well achieved with drugs that oppose the RAAS, as is the case in the black population.


   Disclosures
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 Disclosures
References
 
None.


   Acknowledgments
 
These studies were supported in part by a National Institutes of Health grants RO1-HL14159 (M.H.W.) and MO1-RR00750 (General Clinical Research Center of Indiana University Hospital), by the annual funding of INSERM Unit 652, and by a contract between Sanofi-Aventis and INSERM (DRA/T/007/02/P; L.B. and J.P.).

Part of these studies was presented at the XIVth Meeting of the European Society of Hypertension; June 13 to 17 2004; Paris, France; and published in abstract form (J Hypertens 22[Suppl 2]: S216–S217, 2004).

We acknowledge the contribution of Naomi Fineberg (Indiana University Medical Center, Indianapolis, IN), François Sellin (INSERM, Unit 367, Paris, France), and Dominique Laude (INSERM Unit 652, Paris, France) for assistance in the statistical analyses.

L.B. and J.P. thank Howard Pratt (Department of Medicine, Indiana University School of Medicine) for helpful and constructive comments regarding the discussion of our results and Nadine Bouby (INSERM Unité 652), Stéphane Laurent (INSERM Unit 652), and Gilles Chatellier (Hôpital Européen Georges Pompidou, Paris, France) for additional useful comments.


   Footnotes
 
Published online ahead of print. Publication date available at www.cjasn.org.

See the related editorial, "Vasopressin, Urine Concentration, and Hypertension: A New Perspective of an Old Story," on pages 196–197.

Received October 10, 2006. Accepted November 17, 2006.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 Disclosures
 References
 

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