Circulation, Vol 86, 1859-1863, Copyright © 1992 by American Heart Association
S Goto, Y Ikeda, M Murata, M Handa, E Takahashi, A Yoshioka, Y Fujimura, M Fukuyama, S Handa and S Ogawa
BACKGROUND. Shear-induced platelet aggregation (SIPA) is an important
mechanism in thrombogenesis. von Willebrand factor (vWF) binding to
platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet
aggregation under the high shear force probably generated in stenosed
coronary artery. The physiological significance of vWF- dependent SIPA has
not been clarified. METHODS AND RESULTS. Blood samples were collected from
23 normal volunteers. SIPA was continuously monitored using a modified
cone-plate viscometer adapted for measuring the transmitted light intensity
of the material. The effects of low concentrations of epinephrine, ADP, and
collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108
dyne/cm2) force were investigated. All agonists tested enhanced SIPA under
low shear force, whereas only epinephrine augmented SIPA under high shear
force. The maximum extents of SIPA under high shear force in the absence
and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/-
13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor
yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The
monoclonal antibody NMC-4 against vWF, which was shown to inhibit its
binding to GP Ib, completely abolished SIPA under high shear force, even in
the presence of epinephrine. However, this antibody only partially
inhibited SIPA under low shear force. CONCLUSIONS. Our findings suggest
that epinephrine is the agonist that enhances SIPA mediated by vWF through
its specific receptor. This may be clinically important because occlusion
of the coronary artery often occurs in stenosed atherosclerotic vessels
under sympathetic stimulation.
ARTICLES
Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation
Cardiopulmonary Division, School of Medicine, Keio University, Tokyo, Japan.
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