From the Department of Internal Medicine and Division of Cardiovascular
Diseases, Mayo Clinic and Foundation, Rochester, Minn.
Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu
Background—Coronary
endothelial dysfunction is characterized by an
imbalance between endothelium-derived vasodilating and
vasoconstricting factors and coronary vasoconstriction in
response to the endothelium-dependent vasodilator
acetylcholine. Thus, the present double-blind, randomized study was
designed to test the hypothesis that long-term, 6-month supplementation
of L-arginine, the precursor of the
endothelium-derived vasodilator NO, reverses
coronary endothelial dysfunction to
acetylcholine in humans with nonobstructive coronary
artery disease.
Methods and Results—Twenty-six patients without significant
coronary artery disease on coronary angiography and
intravascular ultrasound were blindly randomized to either oral
L-arginine or placebo, 3 g TID.
Endothelium-dependent coronary blood flow
reserve to acetylcholine (10-6 to 10-4 mol/L)
was assessed at baseline and after 6 months of therapy. There was no
difference between the two study groups in clinical characteristics or
in the coronary blood flow in the response to acetylcholine at
baseline. After 6 months, the coronary blood flow in response
to acetylcholine in the subjects who were taking L-arginine
increased compared with the placebo group (149±20% versus 6±9%,
P<0.05). This was associated with a decrease in plasma
endothelin concentrations and an improvement in patients' symptoms
scores in the L-arginine treatment group compared with the
placebo group.
Conclusions—Long-term oral L-arginine supplementation
for 6 months in humans improves coronary small-vessel
endothelial function in association with a significant
improvement in symptoms and a decrease in plasma endothelin
concentrations. This study proposes a role for L-arginine
as a therapeutic option for patients with coronary
endothelial dysfunction and nonobstructive
coronary artery disease.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Long-term L-Arginine Supplementation Improves Small-Vessel Coronary Endothelial Function in Humans
Key Words: vessels • endothelium • arginine
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