Nitric oxide synthase-dependent responses of the basilar artery during acute infusion of nicotine.
BACKGROUND
Our goals were to determine whether acute exposure to nicotine alters nitric oxide synthase (NOS)-dependent responses of the basilar artery and to identify a potential role for activation of NAD(P)H oxidase in nicotine-induced impairment in NOS-dependent responses of the basilar artery.


METHODS
We measured in vivo diameter of the basilar artery in response to NOS-dependent (acetylcholine) and NOS-independent (nitroglycerin) agonists before and during an acute infusion of nicotine (2 microg/kg/min intravenously for 30 min followed by a maintenance dose of 0.35 microg/kg/min). In addition, we measured superoxide anion production (lucigenin chemiluminescence) by the basilar artery in response to nicotine in the absence or presence of apocynin.


RESULTS
We found that NOS-dependent, but not NOS-independent, vasodilation was impaired during infusion of nicotine. In addition, treatment of the basilar artery with apocynin (100 microM, 30 min prior to infusion of nicotine) prevented nicotine-induced impairment in NOS-dependent vasodilation. Further, the production of superoxide anion was increased in the basilar artery by nicotine, and this increase could be inhibited by apocynin.


CONCLUSIONS
Our findings suggest that acute exposure to nicotine impairs NOS-dependent dilation of the basilar artery by a mechanism that appears to be related to the release of superoxide anion. A possible source of superoxide may be via the activation of NAD(P)H oxidase.
Mayhan
William G
WG
Department of Cellular and Integrative Physiology, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA. wgmayhan@unmc.edu
Arrick
Denise M
DM
Sharpe
Glenda M
GM
Sun
Hong
H
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D049449:Luminescence; D019255:NADPH Oxidases / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D005996:Nitroglycerin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000097:blood / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D013481:Superoxides; D009538:Nicotine; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D005996:Nitroglycerin; D000109:Acetylcholine