Smits P, Temme L, Thien T
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Clin Pharmacol Ther. 1993 Aug;54(2):194-204. doi: 10.1038/clpt.1993.131.
In a placebo-controlled, double-blind randomized design, we investigated the cardiovascular interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing gum) in 10 healthy volunteers, both under baseline conditions and during physical and mental stress (standing up and mental arithmetic). Caffeine alone induced a significant increase in blood pressure associated with a decrease in heart rate, whereas nicotine alone increased both blood pressure and heart rate. The combination of caffeine and nicotine increased systolic and diastolic blood pressure by 10.8 +/- 2.0 and 12.4 +/- 1.9 mm Hg, respectively. This pressor response did not differ significantly from the calculated additive effects of caffeine and nicotine on blood pressure, measuring 12.9 +/- 2.0 and 14.2 +/- 2.1 mm Hg, respectively. Heart rate and forearm blood flow also showed a similar response when the combination of caffeine and nicotine was compared with the calculated sum. During physical stress (standing up), blood pressure, heart rate, and plasma catecholamines increased in the placebo test. The pressor response to standing up was less pronounced after the combination of caffeine and nicotine compared with the sum of the separate effects (combination versus sum: delta diastolic blood pressure, 24.7 +/- 1.9 versus 35.2 +/- 2.6 mm Hg [p < 0.01]; delta mean arterial pressure, 22.1 +/- 2.0 mm Hg versus 28.6 +/- 1.6 mm Hg [p < 0.05]). The plasma catecholamine response did not differ between the combination and the sum of both drugs. During mental arithmetic, blood pressure, heart rate, and forearm blood flow increased in the placebo test. The forearm vasodilator response to mental stress was attenuated by the combination of caffeine and nicotine compared with the sum of both drugs (combination versus sum: delta forearm blood flow, -0.1 +/- 0.3 versus 1.4 +/- 0.5 ml/100 ml/min [p < 0.05]). We conclude that the combined administration of caffeine and nicotine shows additive effects on cardiovascular parameters during baseline conditions but less than additive effects during sympathoadrenal stimulation.
在一项安慰剂对照、双盲随机设计中，我们研究了10名健康志愿者在基线条件下以及在身体和精神应激（站立和心算）期间，咖啡因（静脉注射250毫克）与尼古丁（4毫克口香糖）之间的心血管相互作用。单独使用咖啡因会导致血压显著升高，同时心率降低，而单独使用尼古丁会使血压和心率均升高。咖啡因和尼古丁联合使用使收缩压和舒张压分别升高10.8±2.0和12.4±1.9毫米汞柱。这种升压反应与咖啡因和尼古丁对血压的计算相加效应（分别为12.9±2.0和14.2±2.1毫米汞柱）相比，差异不显著。当将咖啡因和尼古丁联合使用与计算总和进行比较时，心率和前臂血流量也显示出类似的反应。在身体应激（站立）期间，安慰剂测试中血压、心率和血浆儿茶酚胺升高。与单独效应的总和相比，咖啡因和尼古丁联合使用后对站立的升压反应不那么明显（联合使用与总和：舒张压变化，24.7±1.9与35.2±2.6毫米汞柱 [p<0.01]；平均动脉压变化，22.1±2.0毫米汞柱与28.6±1.6毫米汞柱 [p<0.05]）。两种药物联合使用与总和之间的血浆儿茶酚胺反应没有差异。在心算期间，安慰剂测试中血压、心率和前臂血流量增加。与两种药物的总和相比，咖啡因和尼古丁联合使用减弱了对精神应激的前臂血管舒张反应（联合使用与总和：前臂血流量变化，-0.1±0.3与1.4±0.5毫升/100毫升/分钟 [p<0.05]）。我们得出结论，咖啡因和尼古丁联合给药在基线条件下对心血管参数显示出相加效应，但在交感肾上腺刺激期间小于相加效应。
