In vivo and in vitro evidence for impaired arginine transport in human heart failure.
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.


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.
Kaye
D M
DM
Baker Medical Research Institute and Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia. david.kaye@baker.edu.au
Ahlers
B A
BA
Autelitano
D J
DJ
Chin-Dusting
J P
JP
D000328:Adult; D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000097:blood / Q000493:pharmacokinetics*; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics; D005542:Forearm / Q000098:blood supply; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014316:Tritium
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D014316:Tritium; D001120:Arginine