Metoprolol does not reduce platelet aggregability during sympatho-adrenal stimulation.
The possibility that beta-adrenoceptor blockers, especially beta 1-selective agents might inhibit platelet function is of considerable interest, as this might be of pathophysiological importance in cardiovascular diseases. Platelet function, however, is difficult to assess and in vivo related data are scarce. The effect of one week of treatment with metoprolol 200 mg/day on platelet aggregability during mental stress (colour word conflict test; CWT) and low and high dose adrenaline infusions has been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy male volunteers. Platelet function in vivo was assessed using ex vivo filtragometry, and the urinary excretions of beta-thromboglobulin (HMW beta-TG) and 11-dehydro-TxB2 (a thromboxane metabolite). Conventional in vitro aggregometry and the urinary levels of 2,3-dinor-6-keto-PGF1 alpha (a prostacyclin metabolite) were also studied. During the interventions there was increased platelet aggregability in vivo, as filtragometry readings were shortened by 41 +/- 11% during high dose adrenaline infusion, urinary HMW beta-TG levels increased and urinary 11-dehydro-TxB2 tended to increase. In contrast, platelet sensitivity to ADP in vitro was reduced. The urinary 2,3-dinor-6-keto-PGF1 alpha levels were increased during the interventions. Despite the cardiovascular and biochemical signs of beta-adrenoceptor blockade at rest and during the interventions, metoprolol failed to influence platelet function in vivo, as measured by ex vivo filtragometry, or urinary HMW beta-TG or 11-dehydro-TxB2 levels. It tended rather to enhance the stress response measured by ex vivo filtragometry. Platelet aggregability in vitro and urinary 2,3-dinor-6-keto-PGF1 alpha levels were not altered by metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Larsson
P T
PT
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Olsson
G
G
Angelin
B
B
Granström
E
E
Hansson
G
G
Hjemdahl
P
P
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D002395:Catecholamines / Q000652:urine; D004311:Double-Blind Method; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012146:Rest; D013315:Stress, Psychological; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D001620:beta-Thromboglobulin / Q000652:urine
D002395:Catecholamines; D001620:beta-Thromboglobulin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D008790:Metoprolol; D004837:Epinephrine