Cited by 394Smoking Behavior and CessationHeart Rate Variability and Autonomic ControlBlood Pressure and Hypertension Studies

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Mechanisms responsible for sympathetic activation by cigarette smoking in humans.

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Grassi, G, Seravalle, G, Calhoun, D A, Bolla, G B, Giannattasio, C, Marabini, M, Del Bo, A, Mancia, G·1994·Circulation

DOI 10.1161/01.cir.90.1.248

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Abstract

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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Background
Cardiovascular Regulation: Basic Considerations
Mancia, G., Lüscher, T. F., Shepherd, J. T., Noll, G., & Grassi, G. M. (2007) · Springer eBooks · doi:10.1007/978-1-84628-715-2_73 · Cited by 8
Self-citation
Predictors of hemodynamic instability during and persistent after carotid artery stenting
Zhao, H., Wang, Z., Ling, Y., et al. (2023) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2023.107296 · Cited by 7
Management of the Hypertensive Child
Ellis, D. (2009) · Springer eBooks · doi:10.1007/978-3-540-76341-3_63 · Cited by 7
Short‐Term Cigarette Smoking in Rats Impairs Physical Capacity and Induces Cardiac Remodeling
Bocalini, D. S., Luiz, R. D. S., Silva, K. A. S., Serra, A. J., Ávila, R. A., Leopoldo, A. S., Lima‐Leopoldo, A. P., da Cunha, M. R. H., Tucci, P. J. F., & dos SANTOS, L. (2020) · BioMed Research International · doi:10.1155/2020/2589892 · Cited by 11
“For example, it is well known that smoking, or more specifically nicotine, activates the sympathoadrenal system and increases the synthesis and release of noradrenaline and adrenaline [7, 37, 38], and stimulates the renin-angiotensin-aldosterone system [39].”
Background
The Effect of Smoking on the Cardiovascular Autonomic Functions: A Cross Sectional Study
Tayade, M. C. (2013) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2013/5526.3133 · Cited by 7
“Smoking is accompanied by a marked and a prolonged increase in the heart rate and the blood pressure [6].”
Background
The microstructural and functional changes in the macula of heavy habitual smokers
Sobacı, G., Musayev, S., Karslıoğlu, Y., et al. (2013) · International Ophthalmology · doi:10.1007/s10792-013-9716-8 · Cited by 7
Habitual cigarette smoking raises pressor responses to spontaneous bursts of muscle sympathetic nerve activity
Cui, J. G., Drew, R. C., Muller, M. D., Blaha, C., Gonzalez, V., & Sinoway, L. I. (2019) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00293.2018 · Cited by 7
Acute in vivo chylomicron metabolism and postalimentary lipoprotein alterations in normolipidemic male smokers
Zaratin, A. C. M., Bertolami, M. C., Faludi, A. Á., Rocha, J. C., Nunes, V. S., Nakandakare, E. R., Quintão, E. C. R., & de Faria, E. C. (2001) · Clinica Chimica Acta · doi:10.1016/s0009-8981(00)00431-9 · Cited by 7
Insulin Resistance in Smokers and Other Long-Term Users of Nicotine
Eliasson, B., & Smith, U. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-716-1_7 · Cited by 6
Is cardiovascular disease risk in transgender, gender-diverse, and non-binary adults associated with autonomic imbalance?
Miranda, K. T., Schwende, B. K., Duval, A., Streed, C. G., Delage, S. I., Chokly, K., Hodgins, V., & Usselman, C. W. (2025) · Autonomic Neuroscience · doi:10.1016/j.autneu.2025.103283 · Cited by 6
“…use is one of the most clinically relevant modifiable risk factors for the development of CVD. Habitual smokers show elevated sympathetic activity, as measured by MSNA, a proposed link between smoking and heightened CVD risk (Grassi et al., 1994; Hering et al., 2010; Middlekauff et al., 2014).”
The Acute Effect of Cigarette Smoking on QT Dispersion
Khosropanah, S., & Barkat, M. (2015) · Iranian journal of medical sciences · Cited by 6
Wytyczne ESH/ESC dotyczące postępowania w nadciśnieniu tętniczym w 2013 roku
Suplement, K. P. (2013) · Kardiologia Polska · doi:10.5603/kp.2013.0177 · Cited by 7
Therapie und Prophylaxe von Endorgansch�den der Niere
Brandenburg, V. M., Heintz, B., & Floege, J. (2003) · Der Internist · doi:10.1007/s00108-003-0948-y · Cited by 6
“Umgekehrt kommt es zu einer Progressionsverlangsamung der Nierenerkrankung bei Beendigung des Konsums [90, 91, 92, 93].”
Background
Heart Rate Variability and Wavelet-based Studies on ECG Signals from Smokers and Non-smokers
Pal, K., Goel, R., Champaty, B., Samantray, S., & Tibarewala, D. N. (2013) · Journal of The Institution of Engineers (India) Series B · doi:10.1007/s40031-013-0062-z · Cited by 6
Immediate and Sustained Effects of Smoking on Autonomic Arousal in Human Subjects.
McLachlan, C. S., Spence, I., & Satchell, P. M. (1998) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.48.253 · Cited by 6
Effects of Cigarette Smoking on Systemic Hemodynamics
Grassi, G. B., Seravalle, G., Magnoni, M., et al. (2000) · KARGER eBooks · doi:10.1159/000060052 · Cited by 6
Self-citation
Cigarette Smoking Impairs Cardiorespiratory and Metabolic Response at Peak Incremental Exercise and during Recovery in Young, Physically Active Adults
Borrelli, M., Doria, C., Toninelli, N., Longo, S., Coratella, G., Cè, E., Rampichini, S., & Esposito, F. (2024) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003602 · Cited by 7
“Moreover, as part of a cascade effect, there might have occurred a concurrent peripheral sympathetic excitation and an augmented sensitivity of peripheral chemoreceptors as reported in previous studies (57,62).”
Smoking and Kidney Functions
Dönder, A., Balahoroğlu, R., Dülger, H., et al. (2014) · European Journal of Basic Medical Sciences · doi:10.15197/sabad.2.4.04 · Cited by 5
Examining the role of emotion regulation in the bidirectional relation between physiological and subjective stress response among daily cigarette smokers
Borges, A. M., Yang, M.-J., Farris, S. G., Zvolensky, M. J., & Leyro, T. M. (2019) · Personality and Individual Differences · doi:10.1016/j.paid.2019.109740 · Cited by 5
“Regular activation of this system (Grassi et al., 1994; Richards et al., 2011; Trap-Jensen, 1988; Winniford, 1990) may contribute to chronic physiological dysregulation that may be exacerbated or maintained by psychological stress (Dimsdale, 2008) resulting in either elevated or blunted stress…”
Background
Associations of active and passive tobacco exposure with elevated blood pressure in Korean adolescents
Park, H., Jeong, H., Yim, H. W., et al. (2024) · Epidemiology and Health · doi:10.4178/epih.e2024028 · Cited by 5
Cerebral oxygenation and sympathetic responses to smoking in young and middle-aged smokers
Kastelein, T. E., Duffield, R., Crowcroft, S., & Marino, F. E. (2016) · Human & Experimental Toxicology · doi:10.1177/0960327116641736 · Cited by 5
The effect of hidden female smoking on the relationship between smoking and cardiovascular disease
Hwang, S. W., Lee, H. J., Kim, C. H., et al. (2020) · Cardiology Journal · doi:10.5603/cj.a2020.0001 · Cited by 5
“All of these mechanisms are associated with increases in inflammatory markers through the upregulation of arginine vasopressin and endothelin-1 [15].”
Background
The effect of cigarette smoking history on autonomic and cerebral oxygenation responses to an acute exercise bout in smokers
Hartmann, T. E., Marino, F. E., & Duffield, R. (2020) · Physiological Reports · doi:10.14814/phy2.14596 · Cited by 4
Serum Cotinine Levels and Prehypertension in Never Smokers
Alshaarawy, O., Xiao, J., Andrew, M. E., Burchfiel, C. M., & Shankar, A. (2013) · International Journal of Hypertension · doi:10.1155/2013/284524 · Cited by 5
“A vasoconstriction mediated by nicotine is initially responsible for acute but transient increase in the systolic BP [33].”
Background
Captopril does not Blunt the Sympathoadrenal Response to Cigarette Smoking in Normotensive Humans
Ottesen, M. M., Worck, R. H., & Ibsen, H. (1997) · Blood Pressure · doi:10.3109/08037059709086443 · Cited by 5
C-reactive protein to albumin ratio and radial artery thrombosis post transradial angiography
Bulguroğlu, S., Çalapkulu, Y., Koç, U., et al. (2024) · Biomarkers in Medicine · doi:10.1080/17520363.2024.2345578 · Cited by 4
Leptin −2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population
Hung, W., Tsai, C., Lin, C., et al. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28776 · Cited by 4
Smoking Cessation and the Odds of Developing Hypertension in a Working-Age Male Population: The Impact of Body Weight Changes
Saiki, Y., Otsuka, T., Nishiyama, Y., Kato, K., Asai, K., & Kawada, T. (2024) · The American Journal of Medicine · doi:10.1016/j.amjmed.2024.09.003 · Cited by 7
The Increasing Problem of Resistant Hypertension: We’ll Manage till Help Comes!
Natale, F., Franzese, R., Luisi, E., Mollo, N., Marotta, L., Solimene, A., D’Elia, S., Golino, P., & Cimmino, G. (2024) · Medical Sciences · doi:10.3390/medsci12040053 · Cited by 7
“…smokers more frequently present with malignant hypertension, documented by normal ambulatory BP values and higher daytime BP values at 24 h ambulatory BP monitoring [19] and very variable as smoking causes a sympathetic activation that is associated with an increase in BP for about 30 min [20].”
Background
Morphine and nicotine addiction and withdrawal influence baroreflex sensitivity and blood pressure in two-kidney one clip hypertensive (2K1C) rats
Zeinivand, M., Shamsizadeh, A., Pourshanazari, A., et al. (2014) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2014_143 · Cited by 4
“The BP, systemic vascular resistance and heart rate show acute and prolonged increases induced by cigarette smoking (10, 12).”
Background
A STUDY OF EFFECT OF SMOKING ON BLOOD PRESSURE IN HEALTHY YOUNG ADULTS
Prashanth Babu, G., Mallikarjuna, V., Arun Kumar, S., et al. (2014) · Journal of Evolution of Medical and Dental Sciences · doi:10.14260/jemds/2014/2227 · Cited by 4
Digital artery reconstruction with interposition vein graft: impact on secondary Raynaud’s phenomenon
Park, S. O., Wang, H. W., Han, Y., et al. (2023) · Lara D. Veeken · doi:10.1093/rheumatology/kead524 · Cited by 4
Rein et tabac : revue de la littérature et mise au point
Phan, O., Housseini, Y. E., Burnier, M., & Vogt, B. (2013) · Néphrologie & Thérapeutique · doi:10.1016/j.nephro.2012.09.010 · Cited by 4
Acute effects of smoking on left ventricular function and neuro‐humoral responses in patients with known or suspected ischaemic heart disease
Høilund‐Carlsen, P. F., Marving, J., Gadsbøll, N., Rasmussen, S., LØNBORG‐JENSEN, H., Nielsen, M. D., Christensen, N. J., & Jensen, B. H. (2004) · Clinical Physiology and Functional Imaging · doi:10.1111/j.1475-097x.2004.00551.x · Cited by 4
“Newer studies have confirmed this (Grassi et al., 1994) and demonstrated that baroreceptor mediated inhibition of central sympathetic activity can be blunted by nitroprusside infusion, which reverts a smokinginduced decrease to a sudden increase in muscle sympathetic nerve activity with a further…”
Background
Effect of co-administration of morphine and nicotine on cardiovascular function in two-kidney one clip hypertensive (2K1C) rats
Zeinivand, M., Rahman, M. R., Allatavakoli, M., Shamsizadeh, A., Hassanshahi, G., Rezazadeh, H., & Pourshanazari, A. A. (2013) · Bosnian Journal of Basic Medical Sciences · doi:10.17305/bjbms.2013.2345 · Cited by 4
Thioredoxin as a novel sensitive marker of biological stress response in smoking
Soyama, T., Masutani, H., Hirata, C. L., Iwai‐Kanai, E., & Inamoto, T. (2020) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.19-108 · Cited by 4
“(6,7) 11–13) However, as catecholamine levels are largely influenced by exercise.”
Cardiac Autonomic Dysfunction and Increased Oxidative Stress in Conventional Cigarettes and E-Cigarettes: Heart Rate Variability as a Cardiovascular Predictor
Bernardes, F. S. D. O., Regueiro, E. M. G., Bestetti, R. B., Araujo, S. D. S. P., Sabino, J. P. J., & Durand, M. (2025) · Antioxidants · doi:10.3390/antiox14121516 · Cited by 3
Autonomic cardiac control independently predicts incident hypertension and systolic blood pressure in a multi-ethnic population: the HELIUS study
Bouwmeester, T. A., Vriend, E. M. C., Galenkamp, H., Westerhof, B. E., Collard, D., & van den Born, B. H. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf011 · Cited by 3
Inhibition of muscle sympathetic action potential firing and recruitment patterns following cannabis inhalation in humans
D’Souza, A. W., Thiessen, J. S., Cheung, C. P., Nardone, M., Lee, J. B., Baker, R. E., Shoemaker, J. K., Burr, J. F., & Millar, P. J. (2025) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00135.2025 · Cited by 3
Non-additive effects of electrical stimulation of the dorsolateral prefrontal cortex and the vestibular system on muscle sympathetic nerve activity in humans
McCarthy, B., Datta, S., Sesa‐Ashton, G., Wong, R., Henderson, L. A., Dawood, T., & Macefield, V. G. (2024) · Experimental Brain Research · doi:10.1007/s00221-024-06852-5 · Cited by 3
“Each of these factors have been shown to have effects on sympathetic nerve activity (Fagius and Karhuvaara 1989 ; Grassi et al. 1994; Papadelis et al. 2003 ).”
Background
Nicotine in various delivery systems of it and its effect on the heart-rate variability
Menshov, V. A., Trofimov, A. V., Zagurskaya, A. V., Георгиевна, Б. Н., & Yablonskaya, O. I. (2020) · Practical oncology · doi:10.31917/2104327 · Cited by 4
Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose
Miguel, J. P., Dias, A. D. C., Bettini, N. R., de Sousa, S. A. B. A., Durão, M. P. L., Oliveira, L. V. D. C., Monedeiro, F., Ramalho, L. N. Z., Branco, L. G. S., Sabino, J. P. J., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119498 · Cited by 4
The Effect of Dipping Tobacco on Pulse Wave Analysis among Adult Males
Elemam, A. E., Alla, N. D., Ibrahim, N. M., & Ali, A. B. (2020) · BioMed Research International · doi:10.1155/2020/7382164 · Cited by 3
“This needs to be solidly determined as studies reported controversial findings [7, 32, 33].”
Result
Antihypertensive mechanisms of lipid-lowering drugs: decoding the ‘Rosetta stone's inscriptions'
Grassi, G. M., & Taddei, S. (2001) · Journal of Hypertension · doi:10.1097/00004872-200104000-00002 · Cited by 3
Self-citation

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.
ORCID: Grassi, G
Seravalle, G
Calhoun, D A
Giannattasio, C
Mancia, G
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1994-07
Volume: 90
Issue: 1
Pages: 248-253
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.90.1.248
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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Mechanisms responsible for sympathetic activation by cigarette smoking in humans.

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