Goto S, Ikeda Y, Murata M, Handa M, Takahashi E, Yoshioka A, Fujimura Y, Fukuyama M, Handa S, Ogawa S
Cardiopulmonary Division, School of Medicine, Keio University, Tokyo, Japan.
Circulation. 1992 Dec;86(6):1859-63. doi: 10.1161/01.cir.86.6.1859.
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.
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.
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.
剪切力诱导的血小板聚集（SIPA）是血栓形成的重要机制。已发现血管性血友病因子（vWF）与血小板糖蛋白Ib（GP Ib）结合对于在狭窄冠状动脉中可能产生的高剪切力下的血小板聚集至关重要。vWF依赖性SIPA的生理意义尚未阐明。
从23名正常志愿者采集血样。使用改良的锥板粘度计连续监测SIPA，该粘度计适用于测量材料的透射光强度。研究了低浓度肾上腺素、ADP和胶原在低剪切力（12达因/平方厘米）和高剪切力（108达因/平方厘米）下对SIPA的影响。所有测试的激动剂在低剪切力下均增强SIPA，而仅肾上腺素在高剪切力下增强SIPA。在不存在和存在肾上腺素（10纳克/毫升）的情况下，高剪切力下SIPA的最大程度分别为37.9±11.5%和59.7±13.9%。α2肾上腺素能受体拮抗剂育亨宾（1微克/毫升）拮抗肾上腺素的作用。抗vWF的单克隆抗体NMC - 4被证明可抑制其与GP Ib结合，即使在存在肾上腺素的情况下，也能完全消除高剪切力下的SIPA。然而，该抗体仅部分抑制低剪切力下的SIPA。
我们的研究结果表明，肾上腺素是通过其特异性受体增强由vWF介导的SIPA的激动剂。这可能在临床上具有重要意义，因为在交感神经刺激下，冠状动脉闭塞常发生在狭窄的动脉粥样硬化血管中。
