Document Detail


Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure.
MedLine Citation:
PMID:  10673249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The RALES study showed that spironolactone, added to conventional therapy for chronic heart failure, dramatically reduced mortality. We tested the hypothesis that this benefit was partially due to improvement in endothelial function and/or to amplified suppression of the vascular renin-angiotensin axis. METHODS AND RESULTS: We performed a randomized, placebo-controlled, double-blind crossover study on 10 patients with NYHA class II to III chronic heart failure on standard diuretic/ACE inhibitor therapy, comparing 50 mg/d spironolactone (1 month) versus placebo. Forearm vasculature endothelial function was assessed by bilateral forearm venous occlusion plethysmography using acetylcholine and N-monomethyl-L-arginine (L-NMMA), with sodium nitroprusside as a control vasodilator. Also, vascular ACE activity was assessed by use of angiotensin (Ang) I, with Ang II as a control vasoconstrictor. Spironolactone significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM], 177+/-29% versus 95+/-20%, spironolactone versus placebo; P<0.001), with an associated increase in vasoconstriction due to L-NMMA (-35+/-6% versus -18+/-4%; P<0.05). The Ang I response was also significantly reduced with spironolactone (P<0.05), with Ang II responses unaltered. CONCLUSIONS: Spironolactone improves endothelial dysfunction, increases NO bioactivity, and inhibits vascular Ang I/Ang II conversion in patients with heart failure, providing novel mechanisms for its beneficial effect on cardiovascular mortality.
Authors:
C A Farquharson; A D Struthers
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  101     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-06     Completed Date:  2000-03-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  594-7     Citation Subset:  AIM; IM    
Affiliation:
University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK. c.a.j.farquharson@dundee.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aged
Angiotensin I / metabolism
Angiotensin II / metabolism
Chronic Disease
Cross-Over Studies
Diuretics / administration & dosage*
Double-Blind Method
Endothelium, Vascular / drug effects,  physiopathology*
Enzyme Inhibitors / pharmacology
Forearm / blood supply
Heart Failure / drug therapy*,  metabolism,  physiopathology*
Humans
Male
Middle Aged
Nitric Oxide / metabolism*
Spironolactone / administration & dosage*
Vasodilation / drug effects*
omega-N-Methylarginine / pharmacology
Chemical
Reg. No./Substance:
0/Diuretics; 0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 11128-99-7/Angiotensin II; 17035-90-4/omega-N-Methylarginine; 52-01-7/Spironolactone; 9041-90-1/Angiotensin I

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


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