Circulation, Vol 90, 2853-2858, Copyright © 1994 by American Heart Association
DM Gilligan, JA Panza, CM Kilcoyne, MA Waclawiw, PR Casino and AA Quyyumi
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. METHODS AND
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.
ARTICLES
Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
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