Mechanisms Responsible for Sympathetic Activation by Cigarette Smoking in Humans

The pressor and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. Methods and ResultsIn nine normotensive healthy subjects (age, 33.0±3.5 years, mean±SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood flow and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by highperformance liquid chromatography from 1.0±0.9 to 44.2±7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2±2.3%), heart rate (+30.3±4.7%), calf vascular resistance (+ 12.1±4.9%), plasma norepinephrine (+34.8±7.0%), and plasma epinephrine (+90.5±39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity −31.8±5.1%, P < .01). The reduction was inversely related to the increase in mean arterial pressure (r= −.67, P < .05), but the slope of the relation was markedly less (−54.1±7.5%, P < .05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. ConclusionsThese data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related pressor response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the pressor response.

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