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. 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 ...