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.

We studied the cardiovascular responses to orthostatic and mental stress of 43 healthy subjects who daily received six cups of boiled or filtered coffee and of 21 healthy subjects who abstained from caffeine-containing beverages. All 64 subjects first received six cups of filtered coffee/day for 2 weeks. Then blood pressure (BP) and heart rate (HR) were recorded before, during, and after a "stand upright" test and a mental arithmetic test. Subjects were then randomized to either complete abstinence from caffeine-containing beverages (n = 21), or consumption of six cups of filtered coffee (n = 21), or consumption of six cups of boiled coffee/day (n = 22). The stress tests were repeated after subjects had been on these regimens for 8 weeks. Abstinence from coffee did not affect the responses of BP or HR to orthostatic stress, or the response of BP to mental stress. The increase in HR caused by mental stress was five beats/min less (p = 0.02) in the no-coffee group than in the filtered- (95% confidence interval -8.8 to -1.2) or boiled- (95% confidence interval -8.4 to -0.8) coffee group. It is concluded that elimination of caffeine decreases the HR response to mental stress.