Birkenfeld Andreas L, Schroeder Christoph, Pischon Tobias, Tank Jens, Luft Friedrich C, Sharma Arya M, Jordan Jens
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and Helios Klinikum, Berlin, Germany.
Clin Auton Res. 2005 Jun;15(3):200-6. doi: 10.1007/s10286-005-0270-y.
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.
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.
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).
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.
西布曲明是一种血清素和去甲肾上腺素转运体阻滞剂，是一种常见的辅助性肥胖治疗药物。对健康受试者的急性研究表明，一种抑制性中枢神经机制可能会减弱对交感神经系统的外周刺激作用。这一观点尚未在超重和肥胖患者中得到验证。
我们对BMI≥27至<40kg/m²的高血压患者进行了一项随机对照临床研究。在为期4周的安慰剂导入期后，患者被随机分为四种不同的抗高血压治疗组或安慰剂组。在进行4周的抗高血压治疗后，患者额外接受15mg西布曲明每日一次的治疗，为期3个月。在每个阶段结束时，患者接受心血管自主反射测试和分级头高位倾斜试验。
在安慰剂导入期结束至西布曲明治疗结束之间，平均体重从98.5±4kg降至94.7±4kg（p<0.05）。在安慰剂导入期结束时、抗高血压滴定后（无显著性差异）和西布曲明治疗结束时（无显著性差异），仰卧位血压分别为154±3/80±2、145±3/76±2和150±3/79±2mmHg。在头高位倾斜试验期间，血压受到的影响相似。西布曲明使冷加压试验的收缩压反应减弱（p<0.01）。西布曲明降低了仰卧位低频收缩压振荡（p<0.01）。
西布曲明使静息血压有升高趋势，而交感神经刺激时的血压及低频血压振荡降低。这些矛盾的变化与先前对健康受试者的研究一致，提示存在外周和中枢神经系统机制的联合作用。
