SUPEROXIDE-DISMUTASE RESTORES ENDOTHELIUM-DEPENDENT ARTERIOLAR DILATATION DURING ACUTE INFUSION OF NICOTINE

We previously showed [Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H 2337-H2342, 1997] that nicotine impairs endothelium-dependent arteriol ar dilatation. However, mechanisms that accounted for the effect of ni cotine on endothelium-dependent vasodilatation were not examined. Thus the goal of this study was to examine the role of oxygen radicals in nicotine-induced impairment of arteriolar reactivity. We measured diam eter of cheek pouch resistance arterioles (similar to 50 mu m diameter ) in response to endothelium-dependent (ACh and ADP) and -independent (nitroglycerin) agonists before and after infusion of vehicle or nicot ine in the absence or presence of superoxide dismutase. ACh, ADP, and nitroglycerin produced dose-related dilatation of cheek pouch arteriol es before infusion of vehicle or nicotine. Infusion of vehicle, in the absence or presence of superoxide dismutase (150 U/ml), did not alter endothelium-dependent or -independent arteriolar dilatation. In contr ast, infusion of nicotine (2 mu g . kg-1 min-1) impaired endothelium-d ependent, but not -independent, arteriolar dilatation. In addition, th e effect of nicotine on endothelium-dependent vasodilatation was rever sed by topical application of superoxide dismutase. We suggest that ni cotine impairs endothelium-dependent arteriolar dilatation via an incr ease in the synthesis/release of oxygen-derived free radicals.