title: Different effects of calcium antagonists, nitrates, and beta-blockers on platelet function. Possible importance for the treatment of unstable angina.
abstract: BACKGROUND
  The three major classes of antianginal drug all inhibit platelet aggregation at high concentrations in vitro, but detecting clinically relevant effects has proved to be more difficult. We used whole-blood flow cytometry, a sensitive method that allows direct measurement of activation antigens on the surface of individual platelets in whole unfixed blood, to evaluate the effect of representative antianginal drugs on platelet function in vivo in healthy volunteers.
  
  
  RESULTS
  The effects of glyceryl trinitrate (GTN), amlodipine, and atenolol were studied in nine normal volunteers. Fibrinogen binding to activated GP IIb/IIIa and expression of P-selectin, GP Ib, and GP IIb/IIIa on the platelet surface were measured. In addition, fibrinogen binding and P-selectin expression were measured in response to ex vivo stimulation with the agonists ADP and thrombin. The three drugs had very different effects on platelets. GTN inhibited platelet fibrinogen binding and expression of P-selectin at rest and in response to agonist stimulation, whereas amlodipine enhanced P-selectin expression and atenolol increased fibrinogen binding in response to agonists. Atenolol did not block the stimulatory effects of epinephrine on ADP-induced platelet activation. GTN neutralized the proactivatory effects of amlodipine, whereas the effects of atenolol and amlodipine were not additive.
  
  
  CONCLUSIONS
  The three main classes of antianginal medication have different and possible clinically relevant effects on platelet behavior in vivo, nitrates causing inhibition of aggregation (fibrinogen binding) and degranulation (P-selectin expression), calcium antagonists enhancing degranulation, and beta-blockers enhancing aggregation.
authors.affiliation: Department of Cardiology, Royal Brompton Hospital, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Knight
authors.forename: M
authors.initials: M
authors.lastname: Panesar
authors.forename: D J
authors.initials: DJ
authors.lastname: Wilson
authors.forename: N A
authors.initials: NA
authors.lastname: Chronos
authors.forename: D
authors.initials: D
authors.lastname: Patel
authors.forename: K
authors.initials: K
authors.lastname: Fox
authors.forename: A H
authors.initials: AH
authors.lastname: Goodall
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000789:Angina, Unstable / Q000188:drug therapy; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology* / Q000627:therapeutic use; D015539:Platelet Activation / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D017311:Amlodipine; D001262:Atenolol; D005996:Nitroglycerin