Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients--sibutramine and blood pressure.
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.
Birkenfeld
Andreas L
AL
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and Helios Klinikum, Berlin, Germany.
Schroeder
Christoph
C
Pischon
Tobias
T
Tank
Jens
J
Luft
Friedrich C
FC
Sharma
Arya M
AM
Jordan
Jens
J
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
D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine