Acute infusion of nicotine impairs nNOS-dependent reactivity of cerebral arterioles via an increase in oxidative stress.
Our goals were to determine whether acute exposure to nicotine alters neuronal nitric oxide synthase (nNOS)-dependent reactivity of cerebral arterioles and to identify a potential role for oxidative stress in nicotine-induced impairment in nNOS-dependent responses of cerebral arterioles. We measured in vivo diameter of cerebral arterioles to nNOS-dependent (N-methyl-d-aspartate and kainate) and -independent (nitroglycerin) agonists before and during acute treatment with nicotine. We found that nNOS-dependent, but not -independent, vasodilatation was impaired during treatment with nicotine. In addition, treatment of the cerebral microcirculation with tempol (1 h before infusion of nicotine) prevented nicotine-induced impairment in nNOS-dependent vasodilatation. Furthermore, the production of superoxide anion (lucigenin chemiluminescence) was increased in parietal cortex tissue of rats by treatment with nicotine, and this increase in superoxide anion production could be inhibited by tempol. Our findings suggest that acute exposure to nicotine impairs nNOS-dependent dilatation of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide anion.
Arrick
Denise M
DM
Department of Cellular and Integrative Physiology, Omaha, NE 68198-5850, USA.
Mayhan
William G
WG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D018722:Nicotinic Agonists; D013113:Spin Labels; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D016202:N-Methylaspartate; D009538:Nicotine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D005996:Nitroglycerin; D007608:Kainic Acid; C001803:tempol