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(Circulation. 2000;102:2707.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

David M. Kaye, MBBS, PhD; Belinda A. Ahlers, BSc; Dominic J. Autelitano, PhD; Jaye P. F. Chin-Dusting, PhD

From the Baker Medical Research Institute and Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia.

Correspondence to Dr David M. Kaye, Molecular Neurocardiology Laboratory, Baker Medical Research Institute, Commercial Road, Prahran, Victoria 3181, Australia. E-mail david.kaye{at}baker.edu.au

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 [³H]L-arginine (100 nCi/min), forearm clearance of [³H]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, [³H]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/10⁵ 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.

Key Words: amino acids • nitric oxide • radioisotopes • endothelium • cells

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