Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment.
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.
Heusser
Karsten
K
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany.
Engeli
Stefan
S
Tank
Jens
J
Diedrich
Andre
A
Wiesner
Susanne
S
Janke
Juergen
J
Luft
Friedrich C
FC
Jordan
Jens
J
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
D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine