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.


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 micromol/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 micromol/24 h) and during submaximal exercise (2.4+/-1.2 versus 11. 4+/-4.0 micromol/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.
Katz
S D
SD
Columbia Presbyterian Medical Center, Division of Circulatory Physiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Khan
T
T
Zeballos
G A
GA
Mathew
L
L
Potharlanka
P
P
Knecht
M
M
Whelan
J
J
D000328:Adult; D000368:Aged; D001120:Arginine / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism*; D009587:Nitrogen Isotopes; D012016:Reference Values; D012039:Regional Blood Flow; D014508:Urea / Q000378:metabolism / Q000652:urine; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left
D009566:Nitrates; D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D014508:Urea; D001120:Arginine; D003404:Creatinine