Mechanisms responsible for sympathetic activation by cigarette smoking in humans

Background: 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 Results: In 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 high-performance 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. Conclusions: These 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.