Agonist-induced release of nitric oxide during acute exposure to nicotine.
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 microM) and 5'-adenosine diphosphate (ADP; 1.0 microM) during infusion of vehicle and during infusion of nicotine (2.0 microg/kg/min i.v. for 30 minutes followed by a maintenance dose of 0.35 microg/kg/min). In hamsters treated with vehicle, topical application of acetylcholine and ADP elicited reproducible increases in nitric oxide release. In contrast, in hamsters treated with nicotine, there was a marked inhibition of nitric oxide release in response to acetylcholine and ADP. In a previous study (J. Appl. Physiol. 85:1292-1298, 1998) we found that treatment of the hamster cheek pouch microcirculation with superoxide dismutase restored impaired agonist-induced vasodilatation during acute infusion of nicotine. Thus, our second goal was to examine whether superoxide dismutase would restore agonist-induced release of nitric oxide during infusion of nicotine. We found that treatment of the hamster cheek pouch microcirculation with superoxide dismutase prior to infusion of nicotine prevented nicotine-induced impairment of nitric oxide release in response to acetylcholine and ADP. We suggest that nicotine alters dilatation of arterioles via an increased release of superoxide anion and subsequent inactivation of nitric oxide.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA. wgmayhan@unmc.edu
Sharpe
G M
GM
Anding
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009538:Nicotine / Q000378:metabolism / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000378:metabolism / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D009538:Nicotine; D013482:Superoxide Dismutase; D000109:Acetylcholine