Smoking and the Endothelium

Abstract Smoking is the most complex and least understood cardiovascular risk factor. Nicotine effects on the vascular endothelium are related to the functional expression of nicotinic acetylcholine receptors on the endothelial surface. The α-7 nAChR unit is involved in the proliferative effects of nicotine including neovascularization, vascular remodeling, cell migration, proliferation, and differentiation; contributing to atherosclerosis and carcinogenesis. Nicotine promotes functional (endothelial-dependent vasodilation) and structural changes in vascular walls and stimulates catecholamine release, responsible for altering heart rate variability, increasing risk of ventricular and supraventricular arrhythmias, myocardial infarction, and exacerbation of heart failure. Smoking-related endothelial dysfunction is associated with reduced NO bioavailability and increased oxidative stress, as the aromatic compounds of tobacco smoke cause reductions in endogenous antioxidant plasma levels. Smoking-related atherosclerosis is not necessarily due to nicotine, but probably the combined action of various constituents of cigarette smoke; reactive oxygen species from the gas phase contribute to its onset and progression with the most characteristic deleterious result being oxidation of LDL-cholesterol molecules. Vascular smooth muscle cell death due to necrosis is another consequence of the inflammatory process.