Effect of propranolol on platelet function.
Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1-1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.
D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002448:Cell Adhesion / Q000187:drug effects; D003018:Clot Retraction; D003094:Collagen; D006801:Humans; D007536:Isomerism; D010974:Platelet Aggregation / Q000187:drug effects*; D010977:Platelet Factor 3 / Q000378:metabolism; D011433:Propranolol / Q000097:blood / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood
D002250:Carbon Radioisotopes; D012701:Serotonin; D010977:Platelet Factor 3; D000001:Calcimycin; D003094:Collagen; D011433:Propranolol