Document Detail


Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X.
MedLine Citation:
PMID:  12398965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiotensin-converting enzyme (ACE) inhibition has been shown to improve clinical myocardial ischemia in patients with syndrome X (angina pectoris, positive treadmill exercise test, normal coronary angiograms, and no evidence of coronary spasm). This study was conducted to investigate the effects of long-term ACE inhibitors on endothelial nitric oxide (NO) metabolism and coronary microvascular function in patients with syndrome X. After a 2-week washout period, 20 patients with syndrome X were randomized to receive either enalapril, an ACE inhibitor, 5 mg twice daily (n = 10) or placebo (n = 10) in a double-blind design for 8 weeks. Another 6 age- and gender-matched subjects with negative treadmill exercise tests were also studied as controls. Compared with control subjects, patients with syndrome X had significantly reduced coronary flow reserve, reduced plasma levels of nitrate and nitrite (NOx), and a reduced plasma L-arginine to asymmetric dimethylarginine (ADMA) ratio (an index of systemic NO metabolism), as well as reduced endothelial function. These patients also had increased plasma levels of ADMA, which is an endogenous inhibitor of NO synthase and of von Willebrand factor, a marker of endothelial injury. Baseline characteristics including exercise performance and coronary flow reserve were similar between enalapril and placebo groups. After an 8-week treatment period, exercise duration (p = 0.001) and coronary flow reserve (p = 0.001) significantly improved with enalapril but not with placebo. Enalapril treatment, but not placebo, reduced plasma von Willebrand factor (p = 0.03) and ADMA levels (p = 0.01) and increased NOx levels (p = 0.01) and the ratio of L-arginine to ADMA (p <0.01). In patients with syndrome X, the plasma NOx level was positively and ADMA level inversely correlated with coronary flow reserve before and after the treatment. In conclusion, long-term ACE inhibitor treatment with enalapril improved coronary microvascular function as well as myocardial ischemia in patients with syndrome X. This may be related to the improvement of endothelial NO bioavailability with the reduction of plasma ADMA levels.
Authors:
Jaw-Wen Chen; Nai-Wei Hsu; Tao-Cheng Wu; Shing-Jong Lin; Mau-Song Chang
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Evaluation Studies; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  The American journal of cardiology     Volume:  90     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-25     Completed Date:  2002-12-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  974-82     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan. jwchen@vghtpe.gov.tw
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MeSH Terms
Descriptor/Qualifier:
Aged
Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics*
Arginine / analogs & derivatives*,  blood*,  drug effects*
Biological Availability
Coronary Circulation / drug effects*,  physiology*
Double-Blind Method
Enalapril / pharmacokinetics
Endothelium, Vascular / drug effects*,  metabolism*
Exercise Test
Female
Hemodynamics / drug effects
Humans
Male
Microcirculation / drug effects*,  physiology*
Microvascular Angina / blood*,  drug therapy*
Middle Aged
Nitric Oxide / metabolism*
Statistics as Topic
Time
Treatment Outcome
von Willebrand Factor / drug effects
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/von Willebrand Factor; 10102-43-9/Nitric Oxide; 30315-93-6/N,N-dimethylarginine; 74-79-3/Arginine; 75847-73-3/Enalapril

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


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