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. 2023 Jul;475(7):797-805.
doi: 10.1007/s00424-023-02805-z. Epub 2023 Mar 24.

Tobacco smoking and vascular biology and function: evidence from human studies

Omar Hahad  1   2 , Marin Kuntic  3 , Ivana Kuntic  3 , Andreas Daiber  3   4 , Thomas Münzel  3   4
Affiliations

Tobacco smoking and vascular biology and function: evidence from human studies

Omar Hahad et al. Pflugers Arch. 2023 Jul.

Abstract

Tobacco cigarette smoking is among the most complex and least understood health risk factors. A deeper insight into the pathophysiological actions of smoking exposure is of special importance as smoking is a major cause of chronic non-communicable diseases, in particular of cardiovascular disease as well as risk factors such as atherosclerosis and arterial hypertension. It is well known that smoking exerts its negative effects on cardiovascular health through various interdependent pathophysiological actions including hemodynamic and autonomic alterations, oxidative stress, inflammation, endothelial dysfunction, thrombosis, and hyperlipidemia. Importantly, impaired vascular endothelial function is acknowledged as an early key event in the initiation and progression of smoking-induced atherosclerosis. Increasing evidence from human studies indicates that cigarette smoke exposure associates with a pathological state of the vascular endothelium mainly characterized by reduced vascular nitric oxide bioavailability due to increased vascular superoxide production. In the present overview, we provide compact evidence on the effects of tobacco cigarette smoke exposure on vascular biology and function in humans centered on main drivers of adverse cardiovascular effects including endothelial dysfunction, inflammation, and oxidative stress.

Keywords: Endothelial dysfunction; Human studies; Inflammation; Oxidative stress; Tobacco cigarette smoking.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Method of measuring endothelial function and effects of tobacco smoking on endothelial function in subjects with or without hyperlipidemia. A The acetylcholine (ACh)-dependent vasoreactivity of a forearm conduction vessel after intra-arterial ACh infusion can be used to determine endothelial function, i.e., vessel dilatation or increase in blood flow, in humans (plethysmography of the forearm). Vasodilation is measured by Doppler ultrasound after each cumulative dose of ACh, either by vasodilatation or by an increase in blood flow. Translated and used from references [ 85. ] with permission. Copyright © 2016 The British Pharmacological Society. B Curves for an increase in blood flow as a function of ACh dose in healthy subjects, hypercholesterolemic patients, long-term smokers, and hypercholesterolemic patients who are also smokers. All 3 patient groups have a significantly impaired endothelial function compared to the healthy subjects (shown by the lower increase in blood flow due to ACh). Asterisk (*) shows significant differences from starting point; hash (#) indicates significant differences versus healthy subjects (P<0.05). Values estimated and traced from reference [36] with permission Copyright © 1996, Wolters Kluwer Health
Fig. 2
Fig. 2
Effects of tobacco smoking on endothelial function (using forearm plethysmography) in volunteers and antioxidant interventions. A Endothelial function in tobacco smokers, i.e., the vasodilator capacity in response to intraarterial infusion of the endothelium-dependent vasodilator acetylcholine (ACh), was strikingly reduced in chronic smokers (history of more than 20 pack-years) and was restored to normal levels by the administration of the antioxidant vitamin C, compatible with a high degree of oxidative stress in resistance vessels of chronic smokers. In contrast, the administration of vitamin C had no effect in the healthy volunteers. Asterisk (*) shows significant differences from starting point; hash (#) indicates significant differences versus healthy subjects (P<0.05). Values estimated and traced from reference [35] with permission. Copyright © 1996, Wolters Kluwer Health. B Administration of tetrahydrobiopterin (BH4), an essential cofactor of the enzyme endothelial nitric oxide synthase, was able to normalize the impaired endothelial function in tobacco smokers. In the BH4 group of smokers, the ACh-induced increase in blood flow was significantly better than in placebo-treated smokers. Hash (#) indicates significant differences versus smokers (P<0.05). Values estimated and traced from reference [37] with permission. Copyright © 2000, Wolters Kluwer Health
Fig. 3
Fig. 3
Proatherosclerotic molecular mechanisms related to vascular dysfunction. Oxidative stress can be both exogenous (from free radicals in tobacco smoke) and endogenous (from activation of free radical generating enzymes). Superoxide radical (O2-) can originate directly from cigarette smoke or be produced by uncoupled eNOS and NADPH oxidase. NADPH oxidase can be activated by ET-1 through stimulation of PKC, a kinase that activates the subunits of NADPH oxidase, causing it to become assembled and produce superoxide. Superoxide can directly scavenge •NO by forming peroxynitrite (ONOO-) or it can oxidize lipids, such as LDL. This mechanism not only impairs •NO signaling for vasodilation, but also promotes oxidized LDL accumulation in the infiltrated macrophages, propagating atherosclerosis. Created with BioRender.com
Fig. 4
Fig. 4
Mechanisms of increased blood pressure in chronic smokers. ED is initiated and propagated by smoking. Clinical studies have demonstrated increased blood pressure and vascular stiffness, and decreased flow-mediated dilation (FMD) in subjects after smoking only one cigarette, but also in chronic smokers. The increase in secreted adhesion molecules (ICAM-1 and VCAM-1) promotes immune cell infiltration into the endothelium. Accumulated immune cells impair vascular function through decrease in nitric oxide (•NO) signaling, promoting increased vasoconstriction and future atherosclerosis. Created with BioRender.com
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