Circulation, Vol 89, 1951-1957, Copyright © 1994 by American Heart Association
PT Larsson, NH Wallen and P Hjemdahl
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. METHODS AND 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.
ARTICLES
Norepinephrine-induced human platelet activation in vivo is only partly counteracted by aspirin
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
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