title: Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment.
abstract: BACKGROUND
  The serotonin and norepinephrine transporter inhibitor sibutramine is a widely used antiobesity drug. In acute studies, the peripheral sympathomimetic effect of sibutramine was counteracted by a central sympatholytic action.
  
  
  OBJECTIVE
  The objective was to test the hypothesis that blood pressure responses to long-term sibutramine therapy may be related to sympathetic nerve traffic before treatment in a prospective open-label study in an academic clinical research center.
  
  
  METHODS
  This study comprised 20 obese subjects (body mass index, 30-40 kg/m2; age, 30-57 yr) receiving 5 d of placebo treatment followed by open-label 15 mg/d sibutramine and hypocaloric diet over 12 wk.
  
  
  METHODS
  Body weight, blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) (microneurography), plasma catecholamines, and adipose tissue gene expression were measured.
  
  
  RESULTS
  Open-label sibutramine treatment decreased body weight 4.1 kg (P<0.01) and MSNA 17 bursts per minute (P=0.001), and increased diastolic blood pressure 3 mm Hg (P<0.05) and heart rate 8 bpm (P<0.01). The change in blood pressure with sibutramine treatment was inversely correlated with initial MSNA (r2=0.34; P<0.01). Chronic sibutramine treatment increased adrenoreceptor gene expression and plasma catecholamines.
  
  
  CONCLUSIONS
  The blood pressure response to sibutramine treatment is related to initial MSNA so that subjects with higher MSNA exhibit a smaller increase or even a decrease in blood pressure. The phenomenon might be explained by a sustained reduction in central sympathetic activity with sibutramine treatment.
authors.affiliation: Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Heusser
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Andre
authors.initials: A
authors.lastname: Diedrich
authors.forename: Susanne
authors.initials: S
authors.lastname: Wiesner
authors.forename: Juergen
authors.initials: J
authors.lastname: Janke
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000328:Adult; D001067:Appetite Depressants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003503:Cyclobutanes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D012044:Regression Analysis; D015431:Weight Loss
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine