This Article Full Text Full Text (PDF) All Versions of this Article: 46/3/481    most recent 01.HYP.0000179582.42830.1dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saha, C. Articles by Pratt, J. H. Search for Related Content PubMed PubMed Citation Articles by Saha, C. Articles by Pratt, J. H. Related Collections Clinical Studies Other Treatment Related Article

(Hypertension. 2005;46:481.)
© 2005 American Heart Association, Inc.

Original Articles

Improvement in Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension

Chandan Saha; George J. Eckert; Walter T. Ambrosius; Tae-Yon Chun; Mary Anne Wagner; Qianqian Zhao; J. Howard Pratt

From the Department of Medicine (C.S., G.J.E., T.-Y.C., M.A.W., Q.Z, J.H.P.), Indiana University School of Medicine, and the Richard L. Roudebush V.A. Medical Center (J.H.P.), Indianapolis, Ind; and the Department of Public Health Sciences (W.T.A.), Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to J. Howard Pratt, MD, 541 Clinical Dr, Indianapolis, IN 46202-5111. E-mail johpratt{at}iupui.edu

Hypertension in blacks is more prevalent and less often controlled than the hypertension of other ethnic groups. We sought to explore the benefit of adding inhibitors of the epithelial sodium channel (ENaC), an aldosterone-regulated site of sodium reabsorption in the distal nephron, to the antihypertensive regimen of black hypertensive patients. In a prospective, randomized, placebo-controlled, double-blind clinical trial, we used a 2-by-2 factorial design with 4 treatment groups: amiloride (a direct inhibitor of ENaC), spironolactone (an aldosterone receptor antagonist), the combination of both drugs, and placebo. The subjects (n=98) had an elevated blood pressure despite treatment that included a diuretic and a calcium channel blocker; the level of plasma renin activity was 0.56 ng/L per second. The primary end points were changes from baseline in systolic and diastolic blood pressure over a 9-week period of treatment. The reductions in systolic and diastolic blood pressures (mm Hg) were, respectively, 9.8±1.6 (SE) and 3.4±1.0 for amiloride (P<0.001) and 4.6±1.6 (P=0.006) and 1.8±1.0 for spironolactone (P=0.07). Treatment with either amiloride or spironolactone or the combination was well tolerated; no patient experienced hyperkalemia. In a substudy, plasma endothelin-1 levels were observed to decrease after 3 weeks of treatment with spironolactone (P<0.001), consistent with a non–ENaC-related potential benefit of spironolactone. In conclusion, treatment with either amiloride or spironolactone can provide an additional reduction in blood pressure in blacks already receiving conventional antihypertensive therapy.

Key Words: sodium channels • aldosterone • ethnicity • endothelin

Related Article:

Improvement of Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension

David G. Warnock and P. Darwin Bell
Hypertension 2005 46: 469-470. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				G. J. Becker, T. D. Hewitson, and A. Chrysostomou Aldosterone in clinical nephrology--old hormone, new questions Nephrol. Dial. Transplant., August 1, 2009; 24(8): 2316 - 2321. [Full Text] [PDF]

				R. Agarwal, P. Alborzi, S. Satyan, and R. P. Light Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP): A Randomized, Controlled Trial Hypertension, March 1, 2009; 53(3): 500 - 507. [Abstract] [Full Text] [PDF]

				J. Wang, Z.-R. Zhang, C.-F. Chou, Y.-Y. Liang, Y. Gu, and H.-P. Ma Cyclosporine stimulates the renal epithelial sodium channel by elevating cholesterol Am J Physiol Renal Physiol, February 1, 2009; 296(2): F284 - F290. [Abstract] [Full Text] [PDF]

				C. E Hills, P. E Squires, and R. Bland Serum and glucocorticoid regulated kinase and disturbed renal sodium transport in diabetes J. Endocrinol., December 1, 2008; 199(3): 343 - 349. [Abstract] [Full Text] [PDF]

				V. Bhalla and K. R. Hallows Mechanisms of ENaC Regulation and Clinical Implications J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1845 - 1854. [Abstract] [Full Text] [PDF]

				B. C. Rossier and L. Schild Epithelial Sodium Channel: Mendelian Versus Essential Hypertension Hypertension, October 1, 2008; 52(4): 595 - 600. [Full Text] [PDF]

				D. A. Calhoun, D. Jones, S. Textor, D. C. Goff, T. P. Murphy, R. D. Toto, A. White, W. C. Cushman, W. White, D. Sica, et al. Resistant Hypertension: Diagnosis, Evaluation, and Treatment: A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research Circulation, June 24, 2008; 117(25): e510 - e526. [Abstract] [Full Text] [PDF]

				D. A. Calhoun, D. Jones, S. Textor, D. C. Goff, T. P. Murphy, R. D. Toto, A. White, W. C. Cushman, W. White, D. Sica, et al. Resistant Hypertension: Diagnosis, Evaluation, and Treatment: A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research Hypertension, June 1, 2008; 51(6): 1403 - 1419. [Abstract] [Full Text] [PDF]

				M. Bertog, J. E. Cuffe, S. Pradervand, E. Hummler, A. Hartner, M. Porst, K. F. Hilgers, B. C. Rossier, and C. Korbmacher Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome J. Physiol., January 15, 2008; 586(2): 459 - 475. [Abstract] [Full Text] [PDF]

				J. H. Pratt A Not-So-Modest Proposal That a "Modest" Increase in Aldosterone Causes Hypertension and More Hypertension, January 1, 2008; 51(1): 39 - 40. [Full Text] [PDF]

				Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]

				L. Bankir, J. Perucca, and M. H. Weinberger Ethnic Differences in Urine Concentration: Possible Relationship to Blood Pressure Clin. J. Am. Soc. Nephrol., March 1, 2007; 2(2): 304 - 312. [Abstract] [Full Text] [PDF]

				D. A. Calhoun Aldosteronism and Hypertension Clin. J. Am. Soc. Nephrol., September 1, 2006; 1(5): 1039 - 1045. [Abstract] [Full Text] [PDF]

				M. P. Ponda and T. H. Hostetter Aldosterone Antagonism in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 668 - 677. [Full Text] [PDF]

				K. Nagata, K. Obata, J. Xu, S. Ichihara, A. Noda, H. Kimata, T. Kato, H. Izawa, T. Murohara, and M. Yokota Mineralocorticoid Receptor Antagonism Attenuates Cardiac Hypertrophy and Failure in Low-Aldosterone Hypertensive Rats Hypertension, April 1, 2006; 47(4): 656 - 664. [Abstract] [Full Text] [PDF]

				J. H. Pratt Central Role for ENaC in Development of Hypertension J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3154 - 3159. [Abstract] [Full Text] [PDF]

				D. G. Warnock and B. C. Rossier Renal Sodium Handling: The Role of the Epithelial Sodium Channel J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3151 - 3153. [Full Text] [PDF]

				D. G. Warnock and P. D. Bell Improvement of Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension Hypertension, September 1, 2005; 46(3): 469 - 470. [Full Text] [PDF]