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

Background-The clinical features of congestive heart failure (CHF) result f rom a complex interaction between reduced ventricular function, neurohormon al activation, and impaired endothelial function. Although endothelial dysf unction has been well documented, the mechanisms that contribute to this ab normality remain unknown. Recent studies, however, indicate a potential the rapeutic role for supplemental L-arginine, suggesting the presence of an un derlying 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 [H-3]L-arginine (100 nCi/min), forearm clearanc e of [H-3]L-arginine was significantly reduced in CHF patients compared wit h forearm kinetics in control subjects (64+/-2 versus 133+/-14 mL/min, P=0. 002). In conjunction with this, [H-3]L-arginine uptake by peripheral blood mononuclear cells (PBMCs) was also substantially reduced in heart failure p atients 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 obse rved a 76% (P<0.01) reduction in mRNA expression for the cationic amino aci d transporter CAT-1, as assessed by ribonuclease protection assay. Conclusions-These data document both in vivo and in vitro evidence for a ma rked depression of L-arginine transport in human CHF and therefore provide an explanation for the restorative actions of supplemental L-arginine on va scular function in CHF.