Abstract
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 α2-adrenergic receptor yohimbine (1 μg/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.
| Original language | English |
|---|---|
| Pages (from-to) | 1859-1863 |
| Number of pages | 5 |
| Journal | Circulation |
| Volume | 86 |
| Issue number | 6 |
| Publication status | Published - 1992 Dec |
Fingerprint
Keywords
- α-receptor
- Epinephrine
- Platelets
- Von Willebrand factor
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation. / Goto, Shinya; Ikeda, Yasuo; Murata, Mitsuru; Handa, Makoto; Takahashi, Eiichi; Yoshioka, Akira; Fujimura, Yoshihiro; Fukuyama, Mayumi; Handa, Shunnosuke; Ogawa, Satoshi.
In: Circulation, Vol. 86, No. 6, 12.1992, p. 1859-1863.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation
AU - Goto, Shinya
AU - Ikeda, Yasuo
AU - Murata, Mitsuru
AU - Handa, Makoto
AU - Takahashi, Eiichi
AU - Yoshioka, Akira
AU - Fujimura, Yoshihiro
AU - Fukuyama, Mayumi
AU - Handa, Shunnosuke
AU - Ogawa, Satoshi
PY - 1992/12
Y1 - 1992/12
N2 - 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 α2-adrenergic receptor yohimbine (1 μg/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.
AB - 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 α2-adrenergic receptor yohimbine (1 μg/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.
KW - α-receptor
KW - Epinephrine
KW - Platelets
KW - Von Willebrand factor
UR - http://www.scopus.com/inward/record.url?scp=0026574793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026574793&partnerID=8YFLogxK
M3 - Article
C2 - 1360339
AN - SCOPUS:0026574793
VL - 86
SP - 1859
EP - 1863
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 6
ER -