title: Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients--sibutramine and blood pressure.
abstract: BACKGROUND
  Sibutramine, a serotonin and norepinephrine transporter blocker, is a common adjunctive obesity treatment. Acute studies in healthy subjects suggested that an inhibitory central nervous mechanism might attenuate the peripheral stimulatory effect on the sympathetic nervous system. This notion has not been tested in overweight and obese patients.
  
  
  METHODS
  We conducted a randomized, controlled clinical study in hypertensive patients with BMI > or = 27 to < 40 kg/m(2). After 4 week placebo run-in period patients were randomized to four different antihypertensive treatments or placebo. After 4 weeks of antihypertensive therapy, patients were additionally treated with sibutramine 15 mg o. d. for 3 months. Patients underwent cardiovascular autonomic reflex testing and a graded head-up tilt test at the end of each phase.
  
  
  RESULTS
  Mean body weight decreased from 98.5+/-4 to 94.7+/-4 kg (p<0.05) between end of placebo run-in and end of sibutramine treatment. Supine blood pressure was 154+/-3/80+/-2, 145+/-3/76+/-2 and 150+/-3/79+/-2mmHg at the end of placebo run-in, after antihypertensive titration (ns) and end of sibutramine treatment (ns), respectively. Blood pressure was affected similarly during head up tilt testing. The systolic blood pressure response to cold pressor testing was diminished with sibutramine (p<0.01). Sibutramine decreased low frequency systolic blood pressure oscillations in the supine position (p<0.01).
  
  
  CONCLUSIONS
  Resting blood pressure tends to increase with sibutramine, whereas blood pressure during sympathetic stimulation and low frequency blood pressure oscillations are decreased. These paradoxical changes are consistent with previous studies in healthy subjects and suggest a combination of peripheral and central nervous system mechanisms.
authors.affiliation: Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and Helios Klinikum, Berlin, Germany.
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Birkenfeld
authors.forename: Christoph
authors.initials: C
authors.lastname: Schroeder
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001067:Appetite Depressants / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000187:drug effects*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D003503:Cyclobutanes / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D011187:Posture / Q000502:physiology; D016037:Single-Blind Method; D014636:Valsalva Maneuver; D049629:Waist-Hip Ratio
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine