Norepinephrine-induced human platelet activation in vivo is only partly counteracted by aspirin.
BACKGROUND
Epinephrine and mental stress may, via platelet stimulation, enhance the risk of thrombus formation. Norepinephrine is more likely than epinephrine to activate platelets in vivo because of higher levels in plasma but is less well studied in this respect. The antiplatelet drug of choice for patients with coronary artery disease, aspirin, may be less effective during sympathoadrenal activation. We therefore investigated platelet responses in vivo to exogenous norepinephrine with and without aspirin pretreatment.


RESULTS
Platelet aggregability in vivo was assessed in 11 healthy male subjects, by filtragometry ex vivo (which reflects platelet aggregability in vivo) and by measurements of plasma beta-thromboglobulin (beta-TG, which reflects platelet secretion). Norepinephrine infusions elevated venous plasma norepinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced platelet aggregability (filtragometry) concentration dependently (P < .001). Platelet secretion (beta-TG levels) increased during high-dose infusion (P < .01). Aspirin pretreatment (500 mg orally 12 hours earlier) reduced the excretion of 11-dehydrothromboxane B2 by 62 +/- 5% (P < .001) and attenuated platelet aggregability at rest (P < .05) but not the effect of norepinephrine infusion on platelet aggregability. Conversely, resting plasma beta-TG levels and the urinary excretion of high-molecular-weight beta-TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta-TG was abolished.


CONCLUSIONS
Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans. Aspirin may be less effective as an antithrombotic drug during sympathoadrenal activation in humans.
Larsson
P T
PT
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Wallén
N H
NH
Hjemdahl
P
P
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D015444:Exercise / Q000502:physiology; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011292:Premedication; D013564:Sympathetic Nervous System / Q000502:physiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D001620:beta-Thromboglobulin / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D001620:beta-Thromboglobulin; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin; D009638:Norepinephrine