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While we have shown that acute infusion of nicotine impairs agonist-induced dilatation of resistance arterioles (Am.J.Physiol. 272:H2337–H2342, 1997), no studies have examined the release of nitric oxide in response to these agonists before and during treatment with nicotine. Thus, the first goal of the present study was to examine agonist-induced release of nitric oxide by the hamster cheek pouch microcirculation under control conditions and during acute infusion of nicotine. We measured the release of nitric oxide (Sievers NO analyzer) in response to repeated topical application of acetylcholine (1.0 uμM) and 5′-adenosine diphosphate (ADP; 1.0 μM) during infusion of vehicle and during infusion of nicotine (2.0 μg/kg/min iv for 30 minutes followed by a maintenance dose of 0.35 μg/kg/min). In hamsters treated with vehicle, topical application of acetylcholine and ADP elicited reproducible increases in nitric …