title: Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation.
abstract: BACKGROUND
  Endothelium-derived nitric oxide is an important modulator of resting vascular tone in animals and humans. However, the contribution of nitric oxide to exercise-induced vasodilation is unknown.
  
  
  RESULTS
  The effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on exercise-induced vasodilation was studied in 18 healthy subjects (mean +/- SD, 40 +/- 10 years; 10 women). Acetylcholine was used to test the efficacy of L-NMMA in inhibiting stimulation of nitric oxide synthesis and sodium nitroprusside to test the specificity of L-NMMA in inhibiting endothelium-dependent vasodilation. Intermittent handgrip exercise and infusions of acetylcholine and sodium nitroprusside were performed during intra-arterial infusion of 5% dextrose (control) and L-NMMA (4 to 16 mumol/min). Forearm blood flow was determined by strain-gauge plethysmography. Forearm oxygen extraction was measured from arterial and venous oxygen saturations. In a separate study, 10 subjects performed exercise during infusions of 5% dextrose, L-arginine (the substrate for nitric oxide production), and D-arginine (the stereoisomer that is not a substrate for nitric oxide production). L-NMMA reduced exercise blood flow by 7 +/- 13% (P = .04), increased exercise resistance by 18 +/- 20% (P = .02), and increased exercise oxygen extraction by 16 +/- 17% (P < .001). The degree of inhibition of acetylcholine-induced vasodilation with L-NMMA correlated positively with the degree of reduction in exercise blood flow (r = .55, P = .02). The highest dose of L-NMMA (16 mumol/min) produced the greatest effect; exercise blood flow was reduced by 11 +/- 14% (P = .03), and vascular resistance increased by 26 +/- 23% (P = .005). L-NMMA did not affect the forearm vasodilation produced by sodium nitroprusside. Exercise blood flow, resistance, and oxygen extraction were not significantly modified by infusions of either L- or D-arginine.
  
  
  CONCLUSIONS
  Inhibition of nitric oxide synthesis reduces exercise-induced vasodilation in the human forearm, indicating that nitric oxide plays a role in exercise-induced vasodilation. Increased availability of nitric oxide substrate does not enhance exercise-induced vasodilation in healthy subjects. These findings have important implications for disease states in which endothelium-derived nitric oxide production is impaired.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: D M
authors.initials: DM
authors.lastname: Gilligan
authors.forename: J A
authors.initials: JA
authors.lastname: Panza
authors.forename: C M
authors.initials: CM
authors.lastname: Kilcoyne
authors.forename: M A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: P R
authors.initials: PR
authors.lastname: Casino
authors.forename: A A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D005082:Physical Exertion; D012146:Rest; D014664:Vasodilation / Q000502:physiology*; D014666:Vasomotor System / Q000187:drug effects; D019323:omega-N-Methylarginine
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine