Decreased Activity of the l -Arginine–Nitric Oxide Metabolic Pathway in Patients With Congestive Heart Failure

Abstract

Background —Impaired endothelium-dependent, nitric oxide (NO)–mediated vasodilation may contribute to increased vasomotor tone in patients with heart failure. Whether decreased endothelium-dependent, NO-mediated vasodilation in patients with heart failure is due to decreased synthesis or increased degradation of NO is unknown. Methods and Results —To specifically assess the synthetic activity of the l -arginine–NO metabolic pathway, urinary excretion of [ 15 N]nitrates and [ 15 N]urea was determined after a primed continuous intravenous infusion of l -[ 15 N]arginine (40 μmol/kg) in 16 patients with congestive heart failure and 9 age-matched normal control subjects at rest and during submaximal treadmill exercise. After infusion of l -[ 15 N]arginine, 24-hour urinary excretion of [ 15 N]nitrates was decreased in patients with congestive heart failure at rest (2.2±0.5 versus 8.0±2.3 μmol/24 h) and during submaximal exercise (2.4±1.2 versus 11.4±4.0 μmol/24 h) compared with control subjects (both P <0.01). After infusion of l -[ 15 N]arginine, 24-hour urinary excretions of [ 15 N]urea at rest in patients with congestive heart failure and control subjects were not different (1.1±0.3 versus 1.2±0.2 mmol/24 h, P >0.20). Conclusions —A specific decrease in synthetic activity of the l -arginine–NO metabolic pathway contributes to decreased endothelium-dependent vasodilation in patients with congestive heart failure.