From the Cardiology Branch, National Heart, Lung, and Blood Institute
(N.D., D.M.G., A.A.Q.), Bethesda, Md, and Cardiology Division, Department of
Medicine, Jewish General Hospital, McGill University (J.G.D.), Montreal,
Quebec, Canada.
Correspondence to Jean G. Diodati, MD, Cardiology Division, Jewish General Hospital, 3755 Cote Ste-Catherine Rd, Suite E-206, Montreal, Quebec, Canada H3T 1E2. E-mail mc72{at}musica.mcgill.ca
Background—We investigated whether
luminal release of nitric oxide (NO) contributes to inhibition of
platelet activation and whether these effects are reduced in
patients with atherosclerosis.
Methods and Results—Femoral blood flow velocity and ex vivo whole
blood platelet aggregation by impedance aggregometry were measured
in femoral venous blood during femoral arterial infusion of
acetylcholine (ACh; 30 µg/min) in 30 patients, 19 of whom had
angiographic atherosclerosis. Measurements were
repeated with sodium nitroprusside (40 µg/min),
L-arginine (160 µmol/min), and
NG-monomethyl-L-arginine
(L-NMMA; 16 µmol/min). There was significant inhibition of
collagen-induced platelet aggregation with ACh (45±9.5% lower,
P<0.001), and this inhibition was greater in patients
without atherosclerosis (68.7±10.4% reduction) than
in those with atherosclerosis (32.5±8.1%,
P=0.04). The magnitude of inhibition correlated with
vasodilation with ACh, indicating an association between the smooth
muscle and antiplatelet effects of
endothelium-dependent stimulation. Neither L-NMMA nor
sodium nitroprusside altered platelet aggregation.
L-Arginine inhibited platelet aggregation equally in
vitro (34±8% reduction, P<0.01) and in vivo (37±13%
reduction, P<0.01).
Conclusions—Stimulation of NO release into the vascular lumen
with ACh inhibits platelet aggregation, an effect that is
attenuated in patients with atherosclerosis and
endothelial dysfunction. Basal NO release does not
appear to contribute to platelet passivation in vivo.
L-Arginine inhibited platelet aggregation by its direct
action on platelets. These findings provide a
pathophysiological basis for the observed increase
in thrombotic events in atherosclerosis. Use of
L-arginine and other strategies to improve
endothelial NO activity may impact favorably on
thrombotic events in atherosclerosis.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Effect of Atherosclerosis on Endothelium-Dependent Inhibition of Platelet Activation in Humans
Key Words: endothelium • atherosclerosis • blood flow • nitric oxide • platelets
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