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Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects
Author(s) -
Heusser Karsten,
Tank Jens,
Diedrich Andre,
Engeli Stefan,
Klaua Susanne,
Krüger Nadine,
Strauss Anke,
Stoffels Gritt,
Luft Friedrich C.,
Jordan Jens
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2006.02.002
Subject(s) - sibutramine , blood pressure , medicine , heart rate , placebo , baroreflex , anesthesia , crossover study , microneurography , obesity , weight loss , alternative medicine , pathology
Background Sibutramine, a serotonin and norepinephrine transporter blocker, is used as adjunctive obesity treatment. Studies in healthy subjects suggested that sibutramine might have opposing effects on peripheral and central sympathetic activity; an increase in blood pressure has been claimed. Direct measurements of muscle sympathetic nerve activity (MSNA) in sibutramine‐treated patients have not been conducted. Methods and Results Twenty nondiabetic obese men and women completed the study (mean body mass index, 35 ± 3 kg/m 2 ; mean age, 42 ± 8 years). They were treated for 5 days with 15 mg sibutramine per day or matching placebo in a randomized, double‐blind, crossover fashion. At the end of each intervention, heart rate, blood pressure, and MSNA were recorded. Patients underwent cold pressor testing and phenylephrine and nitroprusside infusions. Results The mean blood pressure (systolic/diastolic) was 118 ± 13 mm Hg/70 ± 9 mm Hg with placebo and 120 ± 13 mm Hg/69 ± 8 mm Hg with sibutramine ( P =.29). The mean resting MSNA was 28 ± 14 bursts/min with placebo and 12 ± 10 bursts/min with sibutramine ( P < .0001). Sibutramine attenuated the rise in blood pressure (25 ± 9 mm Hg/9 ± 9 mm Hg versus 31 ± 12 mm Hg/14 ± 9 mm Hg, P < .01) and MSNA (0.3 ± 0.5 arbitrary units/min versus 1.0 ± 1.1 arbitrary units/min, P =.01) in response to cold pressor testing. Baroreflex heart rate control was similar with sibutramine and with placebo. The sympathetic baroreflex was shifted such that at a given blood pressure, MSNA was substantially decreased (top, 44 ± 1.23 bursts/min versus 58 ± 2.99 bursts/min [ P < .001]; center point, 65 ± 0.32 mm Hg versus 67 ± 0.81 mm Hg [ P < .05]). Conclusions Sibutramine treatment profoundly and selectively reduces sympathetic nerve traffic at rest and attenuates the responsiveness to sympathetic stimuli. Our data support the idea that sibutramine's peripheral sympathomimetic effect is counteracted by a central sympatholytic mechanism. Clinical Pharmacology & Therapeutics (2006) 79 , 500–508; doi: 10.1016/j.clpt.2006.02.002