title: Exercise training restores impaired dilator responses of cerebral arterioles during chronic exposure to nicotine.
abstract: Our goal was to determine whether exercise training (ExT) alleviates impaired nitric oxide synthase (NOS)-dependent dilation of pial arterioles during chronic exposure to nicotine. We measured dilation of cerebral (pial) arterioles in sedentary and exercised control and nicotine-treated (2 mg·kg(-1)·day(-1) for 4 wk via an osmotic minipump) rats to an endothelial NOS (eNOS)-dependent (ADP), a neuronal NOS (nNOS)-dependent [N-methyl-D-aspartic acid (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we harvested brain tissue from sedentary and exercised control and nicotine-treated rats to measure the production of superoxide anion and measured superoxide dismutase-1 (SOD-1) protein in cerebral microvessels using Western blot. We found that eNOS-and nNOS-dependent, but not NOS-independent, vasodilation was impaired in nicotine-treated compared with control rats. In addition, the production of superoxide anion (lucigenin chemiluminescence) was increased, and SOD-1 protein decreased, in rats treated with nicotine compared with control rats. Further, although ExT did not significantly affect eNOS- or nNOS-dependent vasodilation in control rats, ExT restored impaired eNOS- and nNOS-dependent responses in nicotine-treated rats. In addition, the increase in superoxide anion production observed in nicotine-treated rats was reduced by ExT, and SOD-1 protein was increased in nicotine-treated rats by ExT. We suggest that ExT restores impaired NOS-dependent dilation of pial arterioles during chronic exposure to nicotine by a mechanism related to the formation of superoxide anion.
authors: Dept. of Cellular and Integrative Physiology, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA. wgmayhan@unmc.edu
authors: William G
authors: WG
authors: Mayhan
authors: Denise M
authors: DM
authors: Arrick
authors: Hong
authors: H
authors: Sun
authors: Kaushik P
authors: KP
authors: Patel
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D005082:Physical Exertion; D010841:Pia Mater / Q000098:blood supply* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018722:Nicotinic Agonists; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D009538:Nicotine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1