Document Detail


Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension.
MedLine Citation:
PMID:  16116042     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 < or =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.
Authors:
Chandan Saha; George J Eckert; Walter T Ambrosius; Tae-Yon Chun; Mary Anne Wagner; Qianqian Zhao; J Howard Pratt
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Review     Date:  2005-08-22
Journal Detail:
Title:  Hypertension     Volume:  46     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-26     Completed Date:  2005-12-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-7     Citation Subset:  IM    
Affiliation:
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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MeSH Terms
Descriptor/Qualifier:
African Continental Ancestry Group*
Amiloride / therapeutic use
Blood Pressure / drug effects*
Epithelial Sodium Channel
Humans
Hypertension / drug therapy,  ethnology*,  physiopathology*
Sodium Channel Blockers / therapeutic use*
Sodium Channels / drug effects*
Spironolactone / therapeutic use
Grant Support
ID/Acronym/Agency:
M01-RR00750/RR/NCRR NIH HHS; R01-HL-3579/HL/NHLBI NIH HHS; R01-HL6730/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Epithelial Sodium Channel; 0/Sodium Channel Blockers; 0/Sodium Channels; 2609-46-3/Amiloride; 52-01-7/Spironolactone
Comments/Corrections
Comment In:
Hypertension. 2005 Sep;46(3):469-70   [PMID:  16116049 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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