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

Circulation. 1999 Apr 27;99(16):2113-7. doi: 10.1161/01.cir.99.16.2113.

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 [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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Arginine / metabolism*
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / physiopathology
  • Creatinine / blood
  • Exercise Test
  • Female
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Humans
  • Leg / blood supply
  • Male
  • Middle Aged
  • Nitrates / metabolism
  • Nitrates / urine
  • Nitric Oxide / metabolism*
  • Nitrogen Isotopes
  • Reference Values
  • Regional Blood Flow
  • Urea / metabolism
  • Urea / urine
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left

Substances

  • Nitrates
  • Nitrogen Isotopes
  • Nitric Oxide
  • Urea
  • Arginine
  • Creatinine