Published online before print November 14, 2002, doi: 10.1161/01.RES.0000047506.52381.90
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Submitted on April 26, 2002
Revised on November 1, 2002
Accepted on November 4, 2002
Reduced Myocardial and Systemic L-Arginine Uptake in Heart Failure
David M. Kaye *;
From Baker Heart Research Institute and Heart Centre, Alfred Hospital, Melbourne, Australia.
* To whom correspondence should be addressed. E-mail: david.kaye{at}baker.edu.au.
Altered nitric oxide (NO) bioavailability has been ascribed an important role in the pathophysiology of congestive heart failure (CHF). In the peripheral vasculature, we recently demonstrated a depression of L-arginine transport in association with pharmacological evidence of reduced endothelial function. In contrast, increased myocardial NO generation has been proposed to account for a component of the reduced myocardial contractility in CHF, although this remains controversial. We determined the whole body clearance rate and cardiac fractional extraction of L-arginine during a steady-state intravenous infusion of [3H]L-arginine (300 nCi/min) in 9 healthy control subjects and 7 patients with moderate to severe CHF. In patients with CHF, there was a 30% reduction in the transcardiac extraction of [3H]L-arginine compared with controls (P<0.05), which was accompanied by a trend toward reduced [3H]L-citrulline release (P=0.06). In conjunction, the systemic clearance rate of [3H]L-arginine was significantly lower in patients with CHF (778±148 versus 1278±144 mL/min, P<0.05). In association with these biochemical indices, we observed a 38% reduction (P<0.05) in the mRNA expression of the cationic amino acid transporter CAT-1 in ventricular myocardial samples from patients with CHF compared with healthy unused donor myocardium, whereas myocardial NOS enzymatic activity and NOS protein were unchanged. These data indicate the presence of a significant reduction in the myocardial uptake of L-arginine in patients with CHF. Furthermore, this abnormality seems to be part of a systemic downregulation of L-arginine transport.
Key words: heart failure • nitric oxide • amino acids • radioisotopes
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