Reduced Myocardial and Systemic l-Arginine Uptake in Heart Failure
作者:
David,
Kaye Melinda,
Parnell Belinda,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 91,
issue 12
页码: 1198-1203
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: heart failure;nitric oxide;amino acids;radioisotopes
数据来源: OVID
摘要:
Abstract—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.
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