DIVERGENT TOLERANCE TO METABOLIC AND CARDIOVASCULAR EFFECTS OF NICOTINE IN SMOKERS WITH LOW AND HIGH-LEVELS OF CIGARETTE CONSUMPTION

Cigarette smokers on average weigh less than nonsmokers. However, amon g smokers, those who smoke the most weigh the most. To better understa nd the effects of nicotine on body weight, we investigated the pharmac odynamics of intravenous nicotine and cigarette smoking in low-level s mokers (10 or fewer cigarettes per day) and high-level smokers (15 to 30 cigarettes per day). Cigarette smoking and intravenous nicotine inc reased heart rate and energy expenditure in most smokers. The effects of intravenous nicotine and smoking were of similar magnitude, confirm ing that the effects of smoking are mediated by nicotine. Nicotine pro duced a slightly greater increase in heart rate in low-level versus hi gh-level smokers, but energy expenditure increased to a much greater e xtent in low-level versus high-level smokers. The plots of plasma nico tine concentration versus responses suggest development of acute toler ance to both heart rate acceleration and increased energy expenditure in low-level smokers; high-level smokers show a similar pattern of tol erance for heart rate but show only a brief increase in energy expendi ture and a hysteresis curve consistent with either rapid development o f tolerance or no effect. Thus there is evidence of differential devel opment or rate of loss of tolerance to cardiovascular versus metabolic effects of nicotine in low-level versus high-level smokers. Pharmacod ynamic differences between low-level and high-level smokers may explai n, at least in part, the unusual relationship between cigarette consum ption and body weight.