Influence of metoprolol treatment on sympatho-adrenal activation of fibrinolysis.
The effects of mental stress (a colour word conflict test, CWT) and adrenaline infusions (0.1 and 0.4 nmol kg-1 min-1) on t-PA activity, t-PA antigen, PAI-1 activity and PAI-1 antigen were studied in 18 healthy male volunteers. Furthermore, the effects of metoprolol (200 mg/day during 1 week) or placebo (double-blind cross-over study) on fibrinolytic responses to sympatho-adrenal activation, and relationships between fibrinolysis and blood lipids were investigated. Low and high dose adrenaline infusions yielding plasma adrenaline levels of 0.9 +/- 0.1 and 3.4 +/- 0.4 nmol/l, respectively, dose-dependently increased t-PA levels with a concomitant decrease in PAI-1 levels. A similar, but weaker, fibrinolytic response seemed to occur during CWT, when plasma adrenaline levels were only moderately increased (to 0.4 +/- 0.1 nmol/l). Metoprolol treatment did not influence the resting levels of the fibrinolytic variables studied, but tended to enhance the t-PA response to CWT and further reduce PAI-1 during adrenaline infusion. Metoprolol treatment was not accompanied by any rise in PAI-1 levels despite drug induced elevations of triglyceride levels. Thus, the present study shows that sympatho-adrenal activation increases fibrinolytic activity in vivo and that metoprolol treatment may have a favourable influence on this activity.
Larsson
P T
PT
Department of Pharmacology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Wiman
B
B
Olsson
G
G
Angelin
B
B
Hjemdahl
P
P
D000311:Adrenal Glands / Q000187:drug effects*; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D015849:Plasminogen Inactivators / Q000032:analysis; D013315:Stress, Psychological / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects*; D010959:Tissue Plasminogen Activator / Q000032:analysis
D008055:Lipids; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator; D008790:Metoprolol; D009638:Norepinephrine; D004837:Epinephrine