Effect of nicotine on endothelium-dependent arteriolar dilatation in vivo

Smoking is a primary risk factor in coronary and peripheral vascular disease. However, the precise component of cigarette smoke that contributes to the pathogenesis of vascular disease remains unclear. The goal of this study was to determine the effect of nicotine on endothelium-dependent dilatation of peripheral resistance arterioles in vivo. We measured the diameter of resistance arterioles (~50 μm in diameter) contained within the microcirculation of the hamster cheek pouch in response to endothelium- dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists before and after an intravenous infusion of vehicle or two concentrations of nicotine. Acetylcholine, ADP, and nitroglycerin produced a dose-related dilatation of the cheek pouch arterioles under control conditions. Endothelium-dependent, but not -independent, dilatation of arterioles was modestly impaired by an infusion of a low concentration of nicotine (1.0 μg·kg^-1·min^-1). Infusion of a higher concentration of nicotine (2 μg·kg^-1·min^-1), which increased the plasma level of nicotine to 14 ± 1.6 ng/ml, produced a profound selective impairment in endothelium-dependent vasodilatation. We suggest that elevations in plasma nicotine may contribute to the pathogenesis of the peripheral vascular disease observed in smokers.