Vascular damage from smoking: disease mechanisms at the arterial wall.

The products of tobacco combustion are absorbed into the systemic circulation. Absorbed nicotine stimulates the release of catecholamines, whilst other products (perhaps including nicotine) injure the arterial endothelium and promote atherogenesis. Free radicals and aromatic compounds diminish the endothelial synthesis of nitric oxide, causing impaired endothelium-dependent relaxation of arteries, the earliest clinical sign of endothelial dysfunction. Smoking alters the shear forces and rheology at the endothelial surface and these changes enhance the effects of products of tobacco combustion to upregulate leucocyte adhesion molecules on the endothelial surface. The increased oxidation of low density lipoprotein (LDL) in smokers has synergistic effects to promote monocyte adhesion and monocyte migration into the subintimal space. Continued stimulation of intimal cells by oxidized LDL leads to the development of atherosclerosis. Many of these effects are ameliorated by high concentrations of vitamin C. Smoking also potentiates thrombosis at the dysfunctional endothelium by increasing the concentration of plasma fibrinogen and altering the activity of platelets. All these proatherogenic effects of smoking to injure the endothelium also are observed, albeit to lesser extent, in passive smokers.