Adrenaline infusion evokes increased thromboxane B2 production by platelets in healthy men: the effect of beta-adrenoceptor blockade.
The effects of direct adrenergic stimulation, achieved by 60-min adrenaline infusion (0.1-0.2 microgram kg-1 min-1), on thromboxane B2 (TxB2) production by platelets in whole blood ex vivo and on ADP-induced platelet aggregation were studied in seven healthy male volunteers. The effects of two beta-adrenergic blocking agents, pindolol and practolol, on the adrenaline-induced changes were furthermore analyzed. Adrenaline administration resulted in an about ten-fold elevation in plasma adrenaline, and an about three-fold increase in TxB2 production by platelets at 30 min of infusion. The increased TxB2 production persisted throughout the entire adrenaline infusion, and up to 30 min of postinfusion period (recovery). Pindolol blunted markedly the effects of adrenaline on platelet TxB2 production, whereas practolol seemed to have only a weak effect. The sensitivity of platelets to ADP-induced aggregation did not change during the 60 min of adrenaline infusion. However, at 60 min of recovery the platelets showed a significantly increased sensitivity to ADP. Correspondingly, pindolol treatment did not affect platelet sensitivity during the infusion period, but at 60 min of recovery it had caused a significantly decreased sensitivity of platelets to ADP-stimulation. Plasma-free fatty acids increased markedly during the adrenaline infusion. This increase was totally blocked by pindolol, but only partly by practolol. The present results demonstrate that adrenaline, at plasma levels seen for example, in complicated myocardial infarction, stimulates platelet TxB2 production and increases the sensitivity of platelets to ADP after the infusion. Pindolol, but not practolol, inhibits these adrenaline-induced changes in platelet behaviour.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011217:Practolol / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D010869:Pindolol; D011217:Practolol; D004837:Epinephrine