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Mechanisms responsible for sympathetic activation by cigarette smoking in humans.
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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.
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“Specifically, nicotine instigates cardiovascular constriction by direct stimulation of epinephrine and norepinephrine release from peripheral sympathetic nerve endings [40].”
From Acute Effects of Nicotine on Physiological and Subjective Sexual Arousal in Nonsmoking Men: A Randomized, Double-Blind, Placebo-Controlled Trial (2008) · cites this paper as [40]
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“The attenuation of physiological sexual arousal following nicotine administration is consistent with literature delineating nicotine’s effects on sympathetic nervous system (SNS) activity.”
From Acute Effects of Nicotine on Physiological and Subjective Sexual Arousal in Nonsmoking Men: A Randomized, Double-Blind, Placebo-Controlled Trial (2008) · cites this paper as [40]
In the citing paper
“These and other studies24,25 indicate that despite the ease of measurement, heart rate cannot be taken as either a marker of cardiac sympathetic adrenergic activity or a reliable indicator of sympathetic activity to other regional circulations.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [24]
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“…renal dysfunction 22,23 , obstructive sleep apnoea 4,24 , overweight/obesity (and its associated insulin resistance) 25–28 , nicotine use (including tobacco cigarettes 29,30 , smokeless tobacco products 29,31 and exposure to second-hand smoke 32 ), psychological stress 33 , and type 2 diabetes 34 .”
Scalise, F., Toscano, E., Sorropago, A., Amman, C., & Grassi, G. M. (2026) · Updates in hypertension and cardiovascular protection · doi:10.1007/978-3-032-29564-4_4
Self-citationWang, X., Han, D. D., Qiu, H., et al. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00407.2026
Denucci, B. L., Isnardo-Fernandes, J., Oliveira, G. C., Neto, S. C., Pinheiro, V. H. S. D., Garrão, N. R., Pinheiro, C. R., de Moura, E. G., Lisboa, P. C., Filgueiras, C. C., et al. (2026) · Physiology & Behavior · doi:10.1016/j.physbeh.2026.115504
Silva, P. E. (2009) · Americanae (AECID Library)
Metadata
- Authors
- Grassi, G., Seravalle, G., Calhoun, D. A., Bolla, G. B., Giannattasio, C., Marabini, M., Del Bo, A., & Mancia, G.
- Affiliations
- Azienda Ospedaliera San Gerardo (IT)
- Cattedra Medicina Interna, Ospedale S. Gerardo dei Tintori, Monza, Italy.
- Venue
- Circulation
- Published
- 1994-07
- Volume
- 90
- Issue
- 1
- Pages
- 248-253
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2034576097
- Cited by
- 394
- References
- 0
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 11 · 2023: 7 · 2022: 9 · 2021: 15 · 2020: 16 · 2019: 12 · 2018: 12 · 2017: 10 · 2016: 14 · 2015: 12 · 2014: 13 · 2013: 26 · 2012: 16
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- National Institutes of Health (5k11hl002568-05, 5k08hl003220-02)
- National Heart, Lung, and Blood Institute (HL 03220, HL02568)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- cigarette smoking, sympathetic nervous system, baroreflex, baroreflex sensitivity, plasma catecholamines, norepinephrine, epinephrine, muscle sympathetic nerve activity, blood pressure, heart rate, vascular resistance, nicotine, hemodynamic response, reflex mechanisms, phenylephrine infusion, normotensive subjects
- MeSH terms
- Adult, Blood Pressure, Female, Heart Rate, Humans, Male, Middle Aged, Muscles, Norepinephrine, Phenylephrine, Smoking, Sympathetic Nervous System
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