Significance of platelet beta-adrenoceptors for platelet responses in vivo and in vitro.
The significance of platelet beta-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the beta-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed alpha- and beta-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma beta-thromboglobulin levels. Adrenaline levels were 3-4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels. beta-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that beta-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an alpha-adrenoceptor mediated proaggregatory action.
Larsson
P T
PT
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Wallén
N H
NH
Martinsson
A
A
Egberg
N
N
Hjemdahl
P
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006403:Hematologic Tests; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D001620:beta-Thromboglobulin / Q000378:metabolism*
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D001620:beta-Thromboglobulin; D000244:Adenosine Diphosphate; D011433:Propranolol; D007545:Isoproterenol; D004837:Epinephrine