The first goal of this study was to determine whether chronic injection of nicotine alters endothelium-dependent arteriolar dilatation. We measured the diameter of cheek pouch resistance arterioles (~50 µm in diameter) in response to endothelium-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in control hamsters and hamsters treated with nicotine (2 µg · kg¹ · day¹ for 2-3 wk). In control hamsters, acetylcholine (0.1 and 1.0 µM) dilated arterioles by 13 ± 2 and 31 ± 3%, respectively, and ADP (1.0 and 10 µM) dilated arterioles by 18 ± 1 and 30 ± 1%, respectively. In contrast, acetylcholine (0.1 and 1.0 µM) dilated arterioles by only 5 ± 2 and 12 ± 3%, respectively, and ADP (1.0 and 10 µM) dilated arterioles by only 7 ± 2 and 13 ± 3%, respectively, in animals treated with nicotine (P < 0.05 vs. response in control hamsters). Nitroglycerin produced similar dose-related dilatation of cheek pouch arterioles in control and nicotine-treated hamsters. Our second goal was to examine a possible mechanism for impaired endothelium-dependent arteriolar dilatation during chronic treatment with nicotine. We found that superfusion of the cheek pouch microcirculation with superoxide dismutase (150 U/ml) restored impaired endothelium-dependent, but did not alter endothelium-independent, arteriolar dilatation in hamsters treated with nicotine. Superfusion with superoxide dismutase did not alter endothelium-dependent or -independent arteriolar dilatation in control hamsters. We suggest that chronic exposure to nicotine produces selective impairment of endothelium-dependent arteriolar dilatation via a mechanism related to the synthesis/release of oxygen-derived free radicals.

acetylcholine; adenosine 5'-diphosphate; nitroglycerin; cheek pouch; hamsters; arterioles; endothelium-derived relaxing factor; oxygen radicals; N^G-monomethyl-L-arginine; nitric oxide

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