title: Inhibition of the renin-angiotensin system does not reduce platelet activity at rest or during stress in hypertension.
abstract: OBJECTIVE
  We investigated the influence of angiotensin receptor blockade and angiotensin-converting enzyme inhibition on stress-induced platelet activation in hypertensive patients. Secondary aims were effects on inflammation, coagulation, and endothelial function.
  
  
  METHODS
  Following a 4-week placebo period, 25 hypertensive patients entered a double-blind, crossover study comparing enalapril (20 mg once daily) and losartan (100 mg once daily) treatment (each for 8 weeks). Patients were studied at rest and after a standardized exercise test.
  
  
  RESULTS
  Mean arterial pressure was reduced from 119 ± 2 to 104 ± 2 (enalapril) and 106 ± 2 (losartan) mmHg (both P <0.001). Plasma angiotensin II decreased from 2.4 ± 0.4 to 0.5 ± 0.1 pmol/l with enalapril, and increased to 7.2 ± 1.3 pmol/l with losartan (both P <0.001). Exercise-evoked platelet activation, as evidenced by increased numbers of P-selectin-positive platelets (P <0.01), elevated circulating platelet-platelet aggregates (P <0.01) and soluble P-selectin levels (P <0.001), and increased platelet responsiveness to adenosine diphosphate and thrombin (both P <0.05). Neither drug influenced these markers of platelet activation at rest or following exercise. Markers of inflammation (high-sensitivity C reactive protein, interleukin-6, tissue necrosis factor-α), coagulation (tissue plasminogen activator antigen, prothrombin fragment F1+2), and endothelial function (von Willebrand factor, soluble vascular cellular adhesion molecule-1, and intercellular adhesion molecule-1) were also uninfluenced by treatment.
  
  
  CONCLUSIONS
  Enalapril and losartan failed to reduce platelet activity both at rest and during exercise in hypertensive patients. Markers of inflammation, coagulation, and endothelial function were similarly unaffected. Inhibition of the renin-angiotensin system promotes its beneficial effects in hypertension through mechanisms other than platelet inhibition.
authors.affiliation: Cardiology Unit, Department of Medicine Solna, Sweden.
authors.forename: Jonas H
authors.initials: JH
authors.lastname: Schwieler
authors.forename: Thomas
authors.initials: T
authors.lastname: Kahan
authors.forename: Nils H
authors.initials: NH
authors.lastname: Wallén
authors.forename: Jürg
authors.initials: J
authors.lastname: Nussberger
authors.forename: Paul
authors.initials: P
authors.lastname: Hjemdahl
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects; D005080:Exercise Test; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012084:Renin-Angiotensin System / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D010919:Placebos; D004656:Enalapril; D019808:Losartan