Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.
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.


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.
Goto
S
S
Cardiopulmonary Division, School of Medicine, Keio University, Tokyo, Japan.
Ikeda
Y
Y
Murata
M
M
Handa
M
M
Takahashi
E
E
Yoshioka
A
A
Fujimura
Y
Y
Fukuyama
M
M
Handa
S
S
Ogawa
S
S
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D013314:Stress, Mechanical; D015016:Yohimbine / Q000494:pharmacology; D014841:von Willebrand Factor / Q000276:immunology / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000911:Antibodies, Monoclonal; D014841:von Willebrand Factor; D015016:Yohimbine; D004837:Epinephrine