Document Detail

L-arginine preferentially dilates stenotic segments of coronary arteries thereby increasing coronary flow.
MedLine Citation:
PMID:  18341529     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND OBJECTIVES: Oxidized LDL cholesterol and cytokines increase arginase and decrease nitric oxide (NO) synthase expression in human endothelial cells, leading to a decrease in NO production. In arteriosclerotic plaques, characterized by increased oxidized LDL and cytokine levels, a sustained local NO reduction might enhance sensitivity of the downstream guanylyl cyclase system towards an acute NO increase. We tested whether application of the NO synthase substrate l-arginine (l-arg, 150 micromol min(-1)) or the NO donor isosorbide dinitrate (ISDN; 0.3 mg) preferentially dilates stenotic coronary artery segments (CS) subsequently increasing poststenotic coronary blood flow (CBF) in patients with coronary artery disease (CAD). DESIGN, SETTING AND SUBJECTS: Changes in coronary diameter and circumferential surface area were assessed by quantitative coronary angiography (QCA) in a nonstenotic upstream segment, the CS, downstream the CS and in a reference vessel (n = 24). CBF was estimated in a subset of 13 patients by QCA and intracoronary Doppler. RESULTS: CS ranged from 62% to 89% (77 +/- 5%). l-arg increased minimal luminal diameter of the stenotic segment from 0.98 +/- 0.06 to 1.14 +/- 0.07 mm (P < 0.05) without affecting other coronary segments. Poststenotic CBF increased by 24 +/- 3%. ISDN dilated all segments again with a predominance of CS (25 +/- 4%) and increased poststenotic CBF by 38 +/- 9%. In a multifactorial anova, a medication with an angiotensin-converting enzyme inhibitor (decreasing inflammation and radical formation) and a ratio of LDL/HDL <3.5 were predictive for an l-arg-induced dilation. CONCLUSION: The increase in poststenotic CBF without affecting nondiseased arteries highlights the therapeutic potential of l-arg in patients with CAD.
T Lauer; P Kleinbongard; J Rath; R Schulz; M Kelm; T Rassaf
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-13
Journal Detail:
Title:  Journal of internal medicine     Volume:  264     ISSN:  1365-2796     ISO Abbreviation:  J. Intern. Med.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-16     Completed Date:  2009-01-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904841     Medline TA:  J Intern Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  237-44     Citation Subset:  IM    
Division of Cardiology, Pulmonology, and Vascular Medicine, Department of Medicine, University Hospital RWTH Aachen, Aachen, Germany.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Arginine / pharmacology,  therapeutic use*
Blood Flow Velocity / drug effects
Coronary Angiography
Coronary Circulation / drug effects*
Coronary Stenosis / drug therapy*,  pathology,  physiopathology,  radiography
Coronary Vessels / drug effects*,  physiopathology
Drug Therapy, Combination
Isosorbide Dinitrate / pharmacology,  therapeutic use
Lipids / blood
Middle Aged
Vasodilation / drug effects*
Vasodilator Agents / pharmacology,  therapeutic use*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Lipids; 0/Vasodilator Agents; 74-79-3/Arginine; 87-33-2/Isosorbide Dinitrate

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

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