Nicotine, the Heart and Blood Vessels

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1. The Papers
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The Papers (22)

Newest first. Study types on this page — Human observational study: 1 · Review: 8 · Animal study: 6 · Cell study: 7. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

New nicotine products and vascular risk

Review, 2025. This review looked at the research on newer nicotine products and their effects on blood vessels, the heart and lungs, metabolism and other parts of health, and at whether they help people stop smoking. The authors report that tobacco use causes 56,124 deaths a year in Spain, one-third of them from heart and blood vessel disease. They found some evidence that these products do less harm than cigarettes to the blood vessels, heart and lungs, and metabolism. However, they found no evidence that switching from cigarettes to these products lowers overall harm, because most users keep smoking as well, they make relapse more likely, they delay or prevent quitting nicotine addiction, and they make it easier for young people to move on to tobacco.

Córdoba García R, Barchilon Cohen V, Lozano Fernández J et al. (2025). New nicotine products and vascular risk. Hipertens Riesgo Vasc. — PubMed PMID: 40946015 · doi:10.1016/j.hipert.2025.07.002

Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy

Animal study, 2021. Researchers exposed pregnant rats to e-cigarette vapor for 1 hour a day, 5 days a week, using liquid with either no nicotine or 18 mg/mL nicotine, and compared them with rats breathing ordinary air. Birth weight and weaning weight did not differ. In the offspring, a main brain artery widened 51% to 56% less in response to a signal from its inner lining, at 1, 3 and 7 months of age. This happened equally with and without nicotine, so the authors concluded that the vapor's base liquid, not nicotine, caused the problem. These results are in rats only.

Burrage EN, Aboaziza E, Hare L et al. (2021). Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy. Am J Physiol Heart Circ Physiol. — PubMed PMID: 34170194 · doi:10.1152/ajpheart.00206.2021

Nicotine promotes angiogenesis in mouse brain after intracerebral hemorrhage

Animal study, 2021. Researchers gave nicotine to mice after a bleed inside the brain (intracerebral hemorrhage), either in their drinking water or as a daily injection. With both methods, nicotine increased the growth of new blood vessels in the damaged area at 7 and 14 days, and it did not make the blood vessels leakier. At 7 days, mice given nicotine also had more surviving nerve cells in the damaged area. Nicotine did not raise levels of a main blood-vessel growth signal (VEGF) and did not draw blood-vessel-forming cells from the bone marrow, so the authors suggest it works through a different route in the brain than in the rest of the body; these results come from mice only.

Matsumoto K, Kinoshita K, Hijioka M et al. (2021). Nicotine promotes angiogenesis in mouse brain after intracerebral hemorrhage. Neurosci Res. — PubMed PMID: 32673702 · doi:10.1016/j.neures.2020.07.003

Nicotine in Senescence and Atherosclerosis

Review, 2020. This review looked at published research on how nicotine and its main breakdown product, cotinine, may affect the heart and blood vessels, apart from the other contents of cigarette smoke. The authors propose that nicotine raises inflammation and oxidative stress through an enzyme called NADPH oxidase 1, and that this pushes smooth muscle cells in artery walls into an aged, non-dividing state called senescence. They say a build-up of these aged cells in the cap covering an artery plaque makes the plaque less stable and worsens atherosclerosis. They conclude that nicotine, and probably cotinine, harm atherosclerosis, but this is a hypothesis drawn from a review of earlier studies, not a new study.

Centner AM, Bhide PG, Salazar G (2020). Nicotine in Senescence and Atherosclerosis. Cells. — PubMed PMID: 32331221 · doi:10.3390/cells9041035

Electronic cigarettes and cardiovascular health: what do we know so far?

Review, 2019. This review looks at what is known about how e-cigarettes affect the heart and blood vessels. The authors note that nicotine is the main biologically active substance in e-cigarette vapor, while the cancer-causing chemicals and burning by-products found in tobacco smoke are very low or undetectable. They describe how tobacco cigarettes harm the heart through inflammation, oxidative damage, clogged arteries, blood clots and nervous-system activation, and they discuss which of these ways of causing harm may also apply to e-cigarette use. They conclude that although e-cigarettes are generally thought to be safer than tobacco cigarettes, their overall effects on heart health are still uncertain, and they discuss the debate between rising e-cigarette use among young people and the use of e-cigarettes to help people quit smoking.

MacDonald A, Middlekauff HR (2019). Electronic cigarettes and cardiovascular health: what do we know so far?. Vasc Health Risk Manag. — PubMed PMID: 31417268 · doi:10.2147/VHRM.S175970

Nicotine and the renin-angiotensin system

Review, 2018. This review looks at how nicotine interacts with the renin-angiotensin system, a hormone system that helps control blood pressure, the heart, the lungs and the nervous system. The authors say the research they reviewed strongly suggests that nicotine pushes this system toward its harmful branch, the ACE/angiotensin II/AT1 receptor pathway, and turns down its protective branch, the ACE2/angiotensin-(1-7)/Mas receptor pathway. They suggest this imbalance may contribute to heart, blood vessel and lung disease. They also point out that e-cigarettes are becoming popular with young adults and youths, and that more research is needed on the heart and lung risks of nicotine.

Oakes JM, Fuchs RM, Gardner JD et al. (2018). Nicotine and the renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. — PubMed PMID: 30088946 · doi:10.1152/ajpregu.00099.2018

Adipocytes promote nicotine-induced injury of endothelial cells via the NF-κB pathway

Cell study, 2017. This laboratory study used human blood-vessel lining cells (endothelial cells) and fat cells grown in dishes to see how nicotine damages blood vessels. Nicotine caused both cell types to die off in a dose-dependent way, meaning more nicotine caused more cell death, and it switched on an inflammation pathway called NF-κB. When the blood-vessel cells were grown together with fat cells, the inflammation signals were stronger and more blood-vessel cells died than when they were grown alone. The authors conclude that fat cells can make blood-vessel injury worse through this pathway, and that the pathway plays a key role in nicotine-induced blood-vessel injury. These results come from cells only, not from animals or people.

Liu X, Wang CN, Qiu CY et al. (2017). Adipocytes promote nicotine-induced injury of endothelial cells via the NF-κB pathway. Exp Cell Res. — PubMed PMID: 28733145 · doi:10.1016/j.yexcr.2017.07.022

Cardiovascular toxicity of nicotine: Implications for electronic cigarette use

Review, 2016. This review looks at whether nicotine itself harms the heart and blood vessels, as part of the debate over the risks of electronic cigarettes. It explains that nicotine has drug effects that could contribute to sudden heart events and faster buildup of artery plaque, the kind seen in cigarette smokers. Studies of nicotine medicines and smokeless tobacco suggest that nicotine without burned tobacco smoke carries a low heart risk compared with smoking, but it is still a concern for people who already have heart disease. The authors report that e-cigarettes, which deliver nicotine without burning tobacco, appear to carry low heart risk in healthy users, at least with short-term use.

Benowitz NL, Burbank AD (2016). Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med. — PubMed PMID: 27079891 · doi:10.1016/j.tcm.2016.03.001

Smokeless tobacco, sport and the heart

Review, 2015. This review looks at smokeless tobacco (snuff and chewing tobacco), which many young athletes use because nicotine can improve some aspects of performance. The authors report that nicotine raises heart rate, blood pressure and the heart's oxygen needs at rest and during moderate exercise. It also lowers heart rate variability, makes irregular heart rhythms more likely, harms the lining of blood vessels and may narrow the heart's arteries during and after exercise, while reducing muscle strength and short bursts of effort. Nicotine may reduce anxiety and improve concentration, agility, aerobic performance and weight control, but it is addictive, and the authors conclude that smokeless tobacco should be discouraged in sport and added to the World Anti-Doping Agency's list of banned substances.

Chagué F, Guenancia C, Gudjoncik A et al. (2015). Smokeless tobacco, sport and the heart. Arch Cardiovasc Dis. — PubMed PMID: 25497687 · doi:10.1016/j.acvd.2014.10.003

Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type

Cell study, 2014. Researchers exposed human aorta smooth muscle cells grown in the lab to a small amount of nicotine for 48 hours to see whether nicotine itself changes how these artery-wall cells behave. After nicotine exposure, markers of the 'synthetic' cell type seen in artery plaques rose (one by 2.93-fold), while markers of the normal 'contractile' type fell (for example to 0.40-fold), and two cell-signaling enzymes became more active. The authors concluded that nicotine can shift these cells toward the plaque-associated type, likely through nicotinic acetylcholine receptors. This result is from cells in a dish only, not from people or animals.

Yoshiyama S, Chen Z, Okagaki T et al. (2014). Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type. Atherosclerosis. — PubMed PMID: 25463075 · doi:10.1016/j.atherosclerosis.2014.10.019

NF-κB pathway mediates vascular smooth muscle response to nicotine

Cell study, 2013. Researchers studied how nicotine affects smooth muscle cells from blood vessel walls. They grew the cells in the lab, either alone or alongside the cells that line blood vessels. Nicotine switched on a signalling pathway called NF-κB, raised the levels of the cells' internal scaffolding proteins and made the cells move more. Blocking the α7 nicotinic receptor or the NF-κB pathway stopped these effects, and the authors conclude that contact signals between the two cell types help the muscle cells respond to nicotine; these results come from cells in a dish only.

Wang Z, Wu W, Tang M et al. (2013). NF-κB pathway mediates vascular smooth muscle response to nicotine. Int J Biochem Cell Biol. — PubMed PMID: 23142498 · doi:10.1016/j.biocel.2012.10.016

Chronic nicotine exposure attenuates proangiogenic activity on human umbilical vein endothelial cells

Cell study, 2011. This laboratory study looked at how nicotine affects human cells that line blood vessels (endothelial cells taken from umbilical cord veins). Short-term nicotine exposure raised the cells' release of nitric oxide, switched on the enzyme that makes it (eNOS), and increased their ability to form new blood vessels. Long-term nicotine exposure reduced this blood-vessel-forming ability, with the cells moving less and forming fewer tube-like structures, but it still protected the cells from dying. The authors connect these effects to changes in eNOS gene activity and nitric oxide production, and the results come from cells only, not from people.

Park HS, Cho K, Park YJ et al. (2011). Chronic nicotine exposure attenuates proangiogenic activity on human umbilical vein endothelial cells. J Cardiovasc Pharmacol. — PubMed PMID: 21383590 · doi:10.1097/FJC.0b013e318206b5d9

Nicotine aggravates the brain postischemic inflammatory response

Animal study, 2011. Researchers gave mice nicotine by injection for 14 days. Their blood nicotine levels reached about 100 ng/ml, which the authors say matches levels in average to heavy smokers. Then they studied what happened when blood flow to the brain was cut off and restored, which models a stroke. Compared with untreated mice, the nicotine-treated mice had more inflammatory signalling molecules in their small brain blood vessels and more white blood cells entering the brain, and they had larger areas of brain damage, worse neurological deficits and a higher death rate. These results come from mice only.

Bradford ST, Stamatovic SM, Dondeti RS et al. (2011). Nicotine aggravates the brain postischemic inflammatory response. Am J Physiol Heart Circ Physiol. — PubMed PMID: 21239632 · doi:10.1152/ajpheart.00928.2010

Cigarette smoking induces atrial fibrosis in humans via nicotine

Human observational study, 2007. Researchers compared heart tissue from 95 people having heart bypass surgery (46 smokers and 49 non-smokers) to see whether smoking is linked to scarring (fibrosis) in the upper chambers of the heart. In smokers, the amount of smoking over the years was the only factor linked to more scarring, and people who developed an irregular heartbeat (atrial fibrillation) after surgery had more scarring. When heart tissue from 8 non-smokers was exposed to nicotine in the laboratory, a scar-building collagen gene became up to 10 times more active, depending on the nicotine dose. The authors conclude that smoking contributes to this heart scarring through nicotine, and note that such scarring may make irregular heart rhythms more likely.

Goette A, Lendeckel U, Kuchenbecker A et al. (2007). Cigarette smoking induces atrial fibrosis in humans via nicotine. Heart. — PubMed PMID: 17395670 · doi:10.1136/hrt.2005.087171

Estrogen down-regulates nicotine-induced adhesion molecule expression via nongenomic signal pathway in endothelial cells

Cell study, 2006. This laboratory study used human endothelial cells taken from umbilical cord veins to look at how estrogen changes the effects of nicotine. In these cells, nicotine raised the levels of adhesion molecules (VCAM-1 and E-selectin), which help white blood cells stick to blood vessel walls. Estrogen lowered these nicotine-driven levels by acting through receptors on the cell surface, using calcium and two signaling pathways (ERK1/2 and p38). The classic estrogen blocker tamoxifen did not stop this effect, and the results come from cells only, not from animals or people.

Wang Y, Wang Z, Wang L et al. (2006). Estrogen down-regulates nicotine-induced adhesion molecule expression via nongenomic signal pathway in endothelial cells. Int Immunopharmacol. — PubMed PMID: 16644474 · doi:10.1016/j.intimp.2005.12.006

Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-alpha, IL-1beta

Cell study, 2004. This laboratory study looked at how nicotine affects immune cells called macrophages and the cells that line blood vessels, using a macrophage cell line and human blood-vessel lining cells taken from umbilical cords. Macrophages treated with nicotine released more of two inflammatory signals, TNF-alpha and IL-1beta, which peaked at a nicotine concentration of 0.06 mM after 24 and 12 hours. Two other signals, IL-8 and IFN-gamma, did not change significantly. When the blood-vessel cells were exposed to fluid from these macrophages, they made more adhesion molecules and let more white blood cells stick to them, and blocking TNF-alpha and IL-1beta stopped this. The authors suggest this may be one way nicotine contributes to blood-vessel dysfunction, but the results come only from cells grown in a dish.

Wang Y, Wang L, Ai X et al. (2004). Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-alpha, IL-1beta. Int Immunopharmacol. — PubMed PMID: 15454119 · doi:10.1016/j.intimp.2004.07.028

Early pathophysiological changes in cerebral vessels predisposing to stroke

Animal study, 2003. Researchers studied rats in three models of conditions linked to stroke: long-term high blood pressure caused by the hormone angiotensin II, long-term nicotine administration, and oxidative injury to the lining of blood vessels. In all three models, muscle cells from small brain arteries showed more activity in L-type calcium channels, along with signs of damage to the vessel lining and increased cell growth in the arteriole walls (a growth-marker index of 70-80%). In the nicotine model, the vessel-lining damage looked like oxidative stress. Drugs that blocked the calcium channels or a related enzyme completely prevented this growth response, which the authors say shows that faulty calcium-channel control drives abnormal vessel-wall growth in these early brain-vessel injuries; these results are from rats only.

Gerzanich V, Ivanova S, Simard JM (2003). Early pathophysiological changes in cerebral vessels predisposing to stroke. Clin Hemorheol Microcirc. — PubMed PMID: 14724353

Nicotine promotes arteriogenesis

Animal study, 2003. Researchers blocked the main leg artery in one leg of 85 rabbits and, for 21 days, delivered nicotine, a known blood-vessel growth factor (basic fibroblast growth factor), or an inactive solution directly into the artery through small implanted pumps. Nicotine increased the number of tiny blood vessels in the starved leg about as much as the growth factor did, and it also improved artery imaging scores, blood pressure in the calf, and blood flow. In lab tests, nicotine made white blood cells called monocytes stick to and cross the blood-vessel lining more readily, and raised several adhesion and signaling molecules two- to three-fold. The authors conclude that, in the short term, nicotine promotes the growth of new blood vessels and arteries in tissue with poor blood supply, but these results come only from rabbits and lab-grown cells, not from people.

Heeschen C, Weis M, Cooke JP (2003). Nicotine promotes arteriogenesis. J Am Coll Cardiol. — PubMed PMID: 12575981 · doi:10.1016/s0735-1097(02)02818-8

Sympathectomy inhibits the vasoactive effects of nicotine in conscious rats

Animal study, 1999. This study in awake rats looked at how nicotine injected into a vein (1 to 100 micrograms per kilogram) raises blood pressure and heart rate. Nicotine raised both, and more so at higher doses. Both effects disappeared when the rats' sympathetic nerve endings were chemically destroyed. Blocking alpha-adrenergic receptors stopped the rise in blood pressure but not the faster heart rate, while blocking vasopressin receptors changed neither. The authors concluded that in rats nicotine raises blood pressure mainly by making blood vessels narrow through noradrenaline-like signals released from nerves rather than from the adrenal glands, and that vasopressin plays no significant role. These results are in animals only.

Marano G, Ramirez A, Mori I et al. (1999). Sympathectomy inhibits the vasoactive effects of nicotine in conscious rats. Cardiovasc Res. — PubMed PMID: 10435011 · doi:10.1016/s0008-6363(98)00326-5

Green tobacco sickness

Review, 1998. This review of medical literature from 1966 to 1998 describes green tobacco sickness, an illness tobacco workers get when nicotine dissolved in the moisture on wet tobacco leaves passes through their skin while they harvest, cut or load the plants. Reported symptoms include weakness, headache, nausea, vomiting, dizziness, stomach cramps, trouble breathing, swings in blood pressure or heart rate, and heavy sweating and drooling. Symptoms start 3 to 17 hours after exposure and last 1 to 3 days. Treatment includes stopping work, changing clothes, showering, drinking fluids and resting, with IV fluids and anti-nausea medicine in more severe cases. The authors say water-resistant protective clothing, chemical-resistant gloves and boots, working in dry conditions, and worker education can lower the risk.

McBride JS, Altman DG, Klein M et al. (1998). Green tobacco sickness. Tob Control. — PubMed PMID: 9825425 · doi:10.1136/tc.7.3.294

Nicotine and sympathetic neurotransmission

Review, 1997. This review explains how nicotine raises heart rate, the force of the heart's pumping and blood pressure. Nicotine switches on nicotinic receptors on nerve endings and in the adrenal glands, which release stress chemicals such as norepinephrine; the review describes step by step how the receptor opens to let sodium and calcium into the cell. In isolated guinea-pig hearts, and in human heart tissue studied in the laboratory, a heart starved of energy released more norepinephrine in response to nicotine. The authors report that this raises the heart's oxygen demand while narrowing its blood vessels, which is especially harmful in people with coronary artery disease and may trigger heart attacks or dangerous heart rhythms.

Haass M, Kübler W (1997). Nicotine and sympathetic neurotransmission. Cardiovasc Drugs Ther. — PubMed PMID: 9110108 · doi:10.1007/BF00053022

The effect of nicotine on cultured cells of vascular origin

Cell study, 1985. Researchers exposed cells grown in the lab from blood vessels to nicotine at a range of concentrations. The cells were lining (endothelial) cells, smooth muscle cells and connective-tissue (fibroblast) cells, taken from healthy pigs, cattle or human fetal tissue. Nicotine increased the production and assembly of the cell's internal scaffolding proteins (the cytoskeleton). The effect was clearest in smooth muscle cells and partly seen in lining cells, while fibroblasts showed no change at the doses tested. These results come only from cells in a dish, not from animals or people.

Csonka E, Somogyi A, Augustin J et al. (1985). The effect of nicotine on cultured cells of vascular origin. Virchows Arch A Pathol Anat Histopathol. — PubMed PMID: 3931344 · doi:10.1007/BF00709990

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1. PubMed: Heart and Blood Vessels and nicotine (the search this page is built from)

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Connections

• Nicotine: The Research
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Metabolism and Weight
• Addiction and Withdrawal
• Patches, Gum and Delivery
• Toxicity and Safety

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