title: Acute and chronic treatment with nicotine impairs reactivity of arterioles in response to activation of potassium channels.
abstract: Although acute and chronic treatment with nicotine impairs nitric oxide synthase-dependent responses of large and small blood vessels, the effect of nicotine on other vasodilator pathways remains uncertain. The goal of the current study was to determine effects of nicotine on dilatation of arterioles to activation of ATP-sensitive potassium channels. Reactivity of cheek pouch arterioles ( approximately 50 microm) was measured during acute (1-2 h) and chronic (2-to 3-week) exposure to nicotine in response to aprikalim, cromakalim, and nitroglycerin. Acute treatment with nicotine impaired dilatation of arterioles in response to aprikalim and cromakalim but not nitroglycerin. Aprikalim and cromakalim (1.0 microM) dilated arterioles by 37 +/- 5% and 30 +/- 3%, respectively, before, but by only 21 +/- 4% and 16 +/- 3%, respectively, after infusion of nicotine (p < 0.05). Chronic exposure to nicotine did not alter vasodilatation to nitroglycerin but impaired vasodilatation to aprikalim and cromakalim. In vehicle-treated hamsters, aprikalim and cromakalim (1.0 microM) dilated arterioles by 28 +/- 1% and 32 +/- 3%, respectively. However, in nicotine-treated hamsters aprikalim and cromakalim (1.0 microM) dilated arterioles by only 3 +/- 1% and 13 +/- 1%, respectively. Next, the role of superoxide anion in impaired responses of arterioles to aprikalim and cromakalim during acute infusion of nicotine was examined. Treatment with superoxide dismutase attenuated the effects of nicotine on aprikalim and cromakalim. Thus, acute and chronic exposure to nicotine has profound affects on vasodilatation to activation of ATP-sensitive potassium channels, which may be mediated by superoxide anion.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA. wgmayhan@unmc.edu
authors.forename: William G
authors.initials: WG
authors.lastname: Mayhan
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D002610:Cheek / Q000098:blood supply / Q000502:physiology; D006224:Cricetinae; D004334:Drug Administration Schedule; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage; D015221:Potassium Channels / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D018722:Nicotinic Agonists; D015221:Potassium Channels; D009538:Nicotine