| In vivo and in vitro evidence for impaired arginine transport in human heart failure. | |
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MedLine Citation:
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PMID: 11094036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D M Kaye; B A Ahlers; D J Autelitano; J P Chin-Dusting |
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Publication Detail:
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Type: Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 102 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2000 Nov |
Date Detail:
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Created Date: 2000-11-30 Completed Date: 2000-12-22 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2707-12 Citation Subset: IM |
Affiliation:
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Baker Medical Research Institute and Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia. david.kaye@baker.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Amino Acid Transport Systems, Basic; 0/Carrier Proteins; 0/Membrane Proteins; 0/RNA, Messenger; 10028-17-8/Tritium; 74-79-3/Arginine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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