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(Circulation. 1999;99:2113-2117.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Decreased Activity of the L-Arginine–Nitric Oxide Metabolic Pathway in Patients With Congestive Heart Failure
From Columbia Presbyterian Medical Center, Division of Circulatory Physiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
Correspondence to Stuart D. Katz, MD, Columbia Presbyterian Medical Center, Division of Circulatory Physiology, Room MHB5-435, 177 Fort Washington Ave, New York, NY 10032.
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 [15N]nitrates and [15N]urea was determined after a primed continuous intravenous infusion of L-[15N]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-[15N]arginine, 24-hour urinary excretion of [15N]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-[15N]arginine, 24-hour urinary excretions of [15N]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.
Key Words: endothelium • vessels • nitric oxide • metabolism • isotopes
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