Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Summary The possibility that β-adrenoceptor blockers, especially β1-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 β-thromboglobulin (HMW β-TG) and 11-dehydro-TxB2 (a thromboxane metabolite). Conventional in vitro aggregometry and the urinary levels of 2,3-dinor-6-keto-PGF1α (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 β-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-PGF1α levels were increased during the interventions. Despite the cardiovascular and biochemical signs of β-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 β-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-PGF1α levels were not altered by metoprolol. Thus, metoprolol was not found to reduce platelet aggregability in healthy male volunteers either at rest or during sympatho-adrenal activation. The effect of treatment may still differ in patients; studies in patients with ischaemic heart disease are under way.
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