Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure

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 [N-15]nitrates and [N-15]urea was determined after a primed continuous intravenous infusion of L-[N-15]arginine (40 mu mol/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-[N-15]arginine, 24-hour urinary excretion of N-15]nitrates was decreased in patients with congestive heart failure at rest (2.2+/-0.5 versus 8.0+/-2.3 mu mol/24 h) and during submaximal exercise (2.4+/-1.2 versus 11.4+/-4.0 mu mol/24 h) compared with control subjects (both P<0.01). After infusion of L-[N-15]arginine, 24-hour urinary excretions of [N-15]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.