Document Detail


In vivo and in vitro evidence for impaired arginine transport in human heart failure.
MedLine Citation:
PMID:  11094036     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The clinical features of congestive heart failure (CHF) result from a complex interaction between reduced ventricular function, neurohormonal activation, and impaired endothelial function. Although endothelial dysfunction has been well documented, the mechanisms that contribute to this abnormality remain unknown. Recent studies, however, indicate a potential therapeutic role for supplemental L-arginine, suggesting the presence of an underlying disorder of L-arginine metabolism. METHODS AND RESULTS: We used 2 complementary approaches to assess L-arginine transport in control subjects and patients with CHF. During a steady-state intra-arterial infusion of [(3)H]L-arginine (100 nCi/min), forearm clearance of [(3)H]L-arginine was significantly reduced in CHF patients compared with forearm kinetics in control subjects (64+/-2 versus 133+/-14 mL/min, P=0.002). In conjunction with this, [(3)H]L-arginine uptake by peripheral blood mononuclear cells (PBMCs) was also substantially reduced in heart failure patients compared with controls (V(max) 10. 1+/-1.3 versus 49.8+/-7.1 pmol/10(5) cells per 5 minutes, P<0.001). In association with this finding, we observed a 76% (P<0.01) reduction in mRNA expression for the cationic amino acid transporter CAT-1, as assessed by ribonuclease protection assay. CONCLUSIONS: These data document both in vivo and in vitro evidence for a marked depression of L-arginine transport in human CHF and therefore provide an explanation for the restorative actions of supplemental L-arginine on vascular function in CHF.
Authors:
D M Kaye; B A Ahlers; D J Autelitano; J P Chin-Dusting
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  102     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-30     Completed Date:  2000-12-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2707-12     Citation Subset:  IM    
Affiliation:
Baker Medical Research Institute and Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia. david.kaye@baker.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Transport Systems, Basic
Arginine / blood,  pharmacokinetics*
Biological Transport
Carrier Proteins / genetics
Forearm / blood supply
Gene Expression Regulation / drug effects
Heart Failure / drug therapy*,  physiopathology
Humans
Leukocytes, Mononuclear / cytology,  drug effects,  metabolism
Membrane Proteins / genetics
Middle Aged
RNA, Messenger / drug effects,  genetics,  metabolism
Regional Blood Flow / drug effects
Time Factors
Tritium / diagnostic use
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems, Basic; 0/Carrier Proteins; 0/Membrane Proteins; 0/RNA, Messenger; 10028-17-8/Tritium; 74-79-3/Arginine

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