Arcavi L, Jacob P, Hellerstein M, Benowitz N L
Division of Clinical Pharmacology and Experimental Therapeutics, San Francisco General Hospital Medical Center, CA.
Clin Pharmacol Ther. 1994 Jul;56(1):55-64. doi: 10.1038/clpt.1994.101.
Cigarette smokers on average weigh less than nonsmokers. However, among smokers, those who smoke the most weigh the most. To better understand the effects of nicotine on body weight, we investigated the pharmacodynamics of intravenous nicotine and cigarette smoking in low-level smokers (10 or fewer cigarettes per day) and high-level smokers (15 to 30 cigarettes per day). Cigarette smoking and intravenous nicotine increased heart rate and energy expenditure in most smokers. The effects of intravenous nicotine and smoking were of similar magnitude, confirming that the effects of smoking are mediated by nicotine. Nicotine produced a slightly greater increase in heart rate in low-level versus high-level smokers, but energy expenditure increased to a much greater extent in low-level versus high-level smokers. The plots of plasma nicotine concentration versus responses suggest development of acute tolerance to both heart rate acceleration and increased energy expenditure in low-level smokers; high-level smokers show a similar pattern of tolerance for heart rate but show only a brief increase in energy expenditure and a hysteresis curve consistent with either rapid development of tolerance or no effect. Thus there is evidence of differential development or rate of loss of tolerance to cardiovascular versus metabolic effects of nicotine in low-level versus high-level smokers. Pharmacodynamic differences between low-level and high-level smokers may explain, at least in part, the unusual relationship between cigarette consumption and body weight.
平均而言，吸烟者的体重比不吸烟者轻。然而，在吸烟者中，吸烟最多的人体重最重。为了更好地理解尼古丁对体重的影响，我们研究了低水平吸烟者（每天吸烟10支或更少）和高水平吸烟者（每天吸烟15至30支）静脉注射尼古丁和吸烟的药效学。吸烟和静脉注射尼古丁会使大多数吸烟者的心率和能量消耗增加。静脉注射尼古丁和吸烟的效果相似，证实了吸烟的效果是由尼古丁介导的。与高水平吸烟者相比，尼古丁使低水平吸烟者的心率升高幅度略大，但与高水平吸烟者相比，低水平吸烟者的能量消耗增加幅度要大得多。血浆尼古丁浓度与反应的关系图表明，低水平吸烟者对心率加快和能量消耗增加均产生了急性耐受性；高水平吸烟者对心率表现出类似的耐受性模式，但能量消耗仅短暂增加，且呈现出与耐受性快速发展或无影响相一致的滞后曲线。因此，有证据表明，低水平吸烟者与高水平吸烟者对尼古丁的心血管效应和代谢效应的耐受性发展或丧失速度存在差异。低水平吸烟者和高水平吸烟者之间的药效学差异可能至少部分解释了吸烟量与体重之间的异常关系。
