Published online before print July 7, 2008, doi: 10.1161/HYPERTENSIONAHA.108.115592
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2008;52:203.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
Ethnic Differences in Renal Handling of Water and Solutes in Hypertension
From the Service de Néphrologie et Consultation d’Hypertension, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Correspondence to Michel Burnier, Service de Néphrologie et Consultation d’Hypertension, Rue du Bugnon 17, CHUV, 1011 Lausanne, Switzerland. E-mail michel.burnier{at}chuv.ch
Ethnic differences in hypertension are well recognized and have been attributed to several factors, including genetic susceptibility, environmental factors, and lifestyle. This latter increases the likelihood of developing hypertension in some populations by favoring the development of risk factors such as obesity, a low level of physical activity, a high sodium intake, and a low dietary intake of potassium and calcium. Thus, high blood pressure is clearly more frequent among black subjects, and hypertensive disease in black subjects differs from that seen in the white population in several aspects: black hypertensive patients more frequently exhibit salt sensitivity, a tendency toward expanded plasma volume, lower plasma renin activity, and increased renal vascular resistance.1,2 Moreover, difference in the urinary excretion of natriuretic and vasodilatory substances, such as dopamine and prostaglandins, and in sodium-potassium and sodium-lithium countertransport have been reported in black and white hypertensive subjects, suggesting once again that subjects of black descent excrete sodium less efficiently than white subjects, an observation that also explains the increased percentage of salt-sensitive hypertension in the black population.3
However, the important unanswered question remains, "Where within the kidney does the greater sodium reabsorption occur?" The characterization of the molecular mechanisms of several monogenic forms of human salt-sensitive hypertension has focused much of the attention on an excessive sodium reabsorption by the distal segments of the nephron.4 However, these forms of hypertension are rare, and so far primary disturbances in distal reabsorption of sodium that could explain the increased sodium sensitivity of hypertension in some populations have not been clearly documented in patients with essential hypertension. Several studies have suggested that an increased reabsorption of sodium by the earlier segments of the nephron may be associated with salt sensitivity.5,6 Thus, Pratt et al7 found that amiloride, an inhibitor of the epithelial sodium channel, had a greater blood pressure–lowering effect in white than in black subjects, indicating that the increased sodium reabsorption in black subjects does not occur in the distal nephron but rather in the proximal segments of the tubule. In another large sample of hypertensive and normotensive black subjects, we found that the ability of the proximal tubule to regulate sodium excretion is a significant determinant of salt sensitivity in humans even after adjustment for several covariates.6 More recently, significant differences in the pattern of proximal and distal tubular sodium reabsorption were found in nuclear families of South Africans or white Belgians, suggesting that black subjects reabsorb more sodium than white subjects in the proximal nephron and less postproximally (J. Staessen, written communication). Taken together, these observations indicate that not only the overall response to sodium administration differs between black and white individuals, but also the segmental renal handling of sodium may differ according to ethnicity.
In this issue of Hypertension, Chun et al8 have added another piece to the puzzle by providing some evidence of an increased activity of the Na,K,2Cl channel in the thick ascending limb in young normotensive subjects of black origin of whom 
25% had a family history of hypertension. In this study, black subjects investigated on a free sodium and water intake had a lower 24-hour urinary volume and more concentrated urine measures than white subjects at baseline. In addition, subjects of African origin exhibited lower urinary excretion rates of potassium, calcium, and magnesium. In this study, Chun et al8 used furosemide as a pharmacological tool to investigate the activity of the Na,K,2Cl channel in vivo. Interestingly, they found a comparable natriuretic effect of furosemide in black and white subjects. However, the response to intravenous furosemide was significantly lower in terms of potassium and calcium excretion, suggesting a greater basal activity of the Na,K,2Cl channel in black subjects. The absence of significant difference in furosemide-induced urinary sodium excretion may seem surprising, but one should take into account that the distal segments of the nephron were still able to adapt for the final elimination of sodium to maintain sodium balance and blood pressure. The data of Chun et al,8 therefore, provide additional evidence that alterations of renal sodium in the loop of Henle segments of the nephron might have some role in the development of hypertension, particularly in black hypertensive subjects. These data should, however, be interpreted with caution. Indeed, whether the response to furosemide solely reflects the activity of the Na,K,2Cl channel could be questioned. Moreover, subjects were not investigated in conditions controlled for sodium, potassium, and calcium intake.
Ethnic differences in the response to antihypertensive therapy are also well recognized.9 Thus, in clinical practice it is generally assumed that diuretics and calcium channel blockers are more effective than blockers of the renin-angiotensin system or β-blockers in lowering blood pressure in black subjects than in white subjects. Yet, dietary salt restriction has been shown to facilitate blood pressure reduction with both blockers of the renin-angiotensin system and calcium antagonists in black subjects, as well as in white hypertensive patients.10 The data of Chun et al8 suggest that some aspects of the acute renal response to a loop diuretic also differ among black and white subjects. Interestingly, the finding of a lower urinary volume and of a significant increase in plasma vasopressin levels in black subjects would suggest that an overactive vasopressin system plays a role in the development of essential hypertension in some subjects of African descent. So far, the use of vasopressin receptor antagonists in the treatment of hypertension has been rather disappointing, but only vasopressin V1 receptor antagonists have been investigated in this clinical indication. If water retention does play a role in the development of hypertension by delaying the excretion of daily ingested fluid and sodium, then partial inhibition of vasopressin V2 receptors with a low dose of a selective V2 receptor antagonist could become an interesting therapeutic approach, as proposed recently by Bankir et al.11 However, this hypothesis remains to be demonstrated.
In conclusion, the data presented by Chun et al8 in this issue confirm the need to investigate in more detail the subtle changes in segmental handling of water and solutes occurring early in hypertensive individuals as it becomes increasingly evident that alterations of sodium excretion in subjects prone to develop essential hypertension do not result from an anomaly of a single transport system but rather from a combination of several subtle changes in sodium reabsorption occurring at different sites along the nephron.
 |
Acknowledgments |
|---|
Disclosures
None.
|
Footnotes |
|---|
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
|
References |
|---|
 Top References |
|---|
1. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986; 8 (suppl II): II-127–II-134.[Medline] [Order article via Infotrieve]
2. Luft FC, Miller JZ, Grim CE, Fineberg NS, Christian JC, Daugherty SA, Weinberger MH. Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological response. Hypertension. 1991; 17: I102–I108.[Medline] [Order article via Infotrieve]
3. Weder AB. Red-cell lithium-sodium countertransport and renal lithium clearance in hypertension. N Engl J Med. 1986; 314: 198–201.[Abstract]
4. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001; 23: 545–555.
5. Chiolero A, Maillard M, Nussberger J, Brunner HR, Burnier M. Proximal sodium reabsorption: an independent determinant of blood pressure response to salt. Hypertension. 2000; 36: 631–637.
6. Burnier M, Bochud M, Maillard M. Proximal tubular function and salt sensitivity. Curr Hypertens Rep. 2006; 8: 8–15.[Medline] [Order article via Infotrieve]
7. Pratt JH, Ambrosius WT, Agarwal R, Eckert GJ, Newman S. Racial difference in the activity of the amiloride-sensitive epithelial sodium channel. Hypertension. 2002; 40: 903–908.
8. Chun T-Y, Bankir L, Eckert GJ, Bichet DG, Saha C, Zaidi S-A, Wagner MA, Pratt JH. Ethnic differences in renal responses to furosemide. Hypertension. 2008; 52: 241–248.
9. Matterson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, Hamburger RJ, Fye C, Lakshman R, Gottdiener J, Ramirez EA, Henderson WG, for the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Single-drug therapy for hypertension in men. N Engl J Med. 1993; 328: 914–921.
10. Weir MR, Chrysant SG, McCarron DA, Canossa-Terris M, Cohen JD, Gunter PA, Lewin AJ, Mennella RF, Kirkegaard LW, Hamilton JH, Weinberger MH, Weder AB. Influence of race and dietary salt on the antihypertensive efficacy of an angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt-sensitive hypertensives. Hypertension. 1998; 31: 1088–1096.
11. Bankir L, Perucca J, Weinberger MH. Ethnic differences in urine concentration: possible relationship to blood pressure. Clin J Am Soc Nephrol. 2007; 2: 304–312.
Related Article:
Hypertension 2008 52: 241-248.
This article has been cited by other articles:
 |
|
 |
|
  P. M. O'Connor, L. Lu, M. Liang, and A. W. Cowley Jr A Novel Amiloride-Sensitive H+ Transport Pathway Mediates Enhanced Superoxide Production in Thick Ascending Limb of Salt-Sensitive Rats, Not Na+/H+ Exchange Hypertension, August 1, 2009; 54(2): 248 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Sanders Dietary Salt Intake, Salt Sensitivity, and Cardiovascular Health Hypertension, March 1, 2009; 53(3): 442 - 445. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||