Document Detail


L-arginine ameliorates the abnormal sympathetic response of the dysfunctional human coronary microvasculature.
MedLine Citation:
PMID:  14759083     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A nitric oxide (NO)-related defect may contribute to abnormal coronary sympathetic responses that can cause ischemia in patients with endothelial dysfunction. Because L-arginine, the NO synthase (NOS) precursor, augments NO bioactivity, we hypothesized that L-arginine would improve dysfunctional coronary sympathetic responses. Eleven patients with atherosclerosis or its risk factors were challenged with the cold pressor test, a specific provocative test of cardiac sympathetic activity, after 3 separate and sequential intracoronary infusions, as follows: 1) Normal saline; 2) L-NMMA, a competitive inhibitor of NOS; and 3) L-arginine. Study patients exhibited abnormal microvascular responses with coronary vascular resistance (CVR) increasing by 22.3 +/- 9.7% (mean +/- 1 SEM), p < 0.01. In addition, the change in coronary blood flow (CBF) did not correlate with the change in rate pressure product (RPP), r = -0.29, p = NS, suggesting an uncoupling of CBF from cardiac work. In the presence of L-NMMA, the CVR response, 10.3 +/- 9.8%, did not differ from the baseline response, and there was no relationship between the changes in CBF and RPP, r = 0.13, p = NS. In contrast, L-arginine ameliorated the CVR response, -3.2 +/- 3.1%, p < 0.05 vs baseline response, and restored the normal correlation between the changes in CBF and RPP, r = 0.74, p < 0.01. L-arginine not only improved abnormal microvascular responses to sympathetic activation, but it also restored the coupling that normally exists between coronary blood flow and cardiac work. L-arginine warrants further investigation as a therapy for coronary artery disease.
Authors:
Joel Gellman; Joshua M Hare; Charles J Lowenstein; Gary Gerstenblith; Vicki Coombs; Patricia Langenberg; Jeffrey A Brinker; Jon R Resar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Angiology     Volume:  55     ISSN:  0003-3197     ISO Abbreviation:  Angiology     Publication Date:    2004 Jan-Feb
Date Detail:
Created Date:  2004-02-04     Completed Date:  2004-02-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0203706     Medline TA:  Angiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. joel_gellman@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Arginine / pharmacology*
Coronary Artery Disease / physiopathology*
Female
Hemodynamics / drug effects
Humans
Male
Microcirculation / drug effects*
Middle Aged
Regional Blood Flow / drug effects
Sympathetic Nervous System / drug effects*
Vascular Resistance / drug effects
omega-N-Methylarginine / pharmacology
Chemical
Reg. No./Substance:
17035-90-4/omega-N-Methylarginine; 74-79-3/Arginine

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


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