Epinephrine and shear stress synergistically induce platelet aggregation via a mechanism that partially bypasses VWF-GP IB interactions.
Elevated shear stress levels in pathologically stenosed vessels induce platelet activation and aggregation, and may play a role in the pathogenesis of arterial disease. Increased plasma catecholamine concentrations have also been implicated in the onset of acute coronary ischemic syndromes. This study was designed to examine the synergistic interaction of shear stress and epinephrine in the activation of platelets. Platelets (in PRP) sheared at 60 dyn/cm2 showed little or no aggregation unless pretreated with epinephrine. Pretreatment with 250 nM epinephrine followed by shear at 60 dyn/cm2 induced > 60% platelet aggregation. The specific alpha 2-adrenergic receptor antagonist yohimbine inhibited the synergistic aggregation, as did the ADP scavenging system phosphocreatine/creatine phosphokinase, indicating a three-way synergism with ADP. Chemical or monoclonal antibody blockade of von Willebrand factor (vWF) interactions with either platelet glycoprotein (Gp) Ib or Gp IIb/IIIa completely inhibited platelet aggregation induced by activating levels of shear stress alone. However, the combination of epinephrine and shear stress induced platelet aggregation that was blocked by 10E5, a monoclonal antibody that inhibits vWF binding to Gp IIb/IIIa, but not by aurin tricarboxylic acid or the monoclonal antibody 6D1, both of which inhibit vWF binding to Gp Ib. Synergistic platelet aggregation in response to epinephrine and shear stress was observed in washed platelets, platelet-rich plasma and whole blood in vitro, and also ex vivo following exercise to elevate endogenous levels of catecholamines. These results indicate that epinephrine synergizes with shear stress to induce platelet aggregation. This synergistic response requires functional Gp IIb/IIIa complexes, but is at least partially independent of vWF-Gp Ib interactions.
Wagner
C T
CT
Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX 77251, USA.
Kroll
M H
MH
Chow
T W
TW
Hellums
J D
JD
Schafer
A I
AI
D002118:Calcium / Q000097:blood; D018929:Cell Culture Techniques; D003402:Creatine Kinase / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D015444:Exercise / Q000502:physiology; D006801:Humans; D007700:Kinetics; D010725:Phosphocreatine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D013314:Stress, Mechanical; D015016:Yohimbine / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism*
D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D010725:Phosphocreatine; D015016:Yohimbine; D003402:Creatine Kinase; D002118:Calcium; D004837:Epinephrine