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Sympathetic Vasomotor Tone Determines Blood Pressure Response to Long-Term Sibutramine Treatment

Franz-Volhard Clinical Research Center (K.H., S.E., J.T., S.W., J.Ja., F.C.L., J.Jo.), Medical Faculty of the Charité and HELIOS Klinikum, 13125 Berlin, Germany; and Autonomic Dysfunction Service (A.D.), Vanderbilt University, Nashville, Tennessee 37232-2195

Address all correspondence and requests for reprints to: Jens Jordan, M.D., Franz-Volhard Clinical Research Center, Haus 129, Charité-Campus Buch, Wiltbergstr. 50, 13125 Berlin, Germany. E-mail: jens.jordan{at}charite.de.

Context: 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.

Patients: 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.

Main Outcome Measures: 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.