Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine.
Our goals were to determine whether chronic exposure to nicotine alters nitric oxide synthase (NOS)-dependent reactivity of cerebral (pial) arterioles and to identify a potential role for NADPH oxidase in impaired NOS-dependent responses during chronic exposure to nicotine. We measured in vivo diameter of pial arterioles to NOS-dependent (acetylcholine and ADP) and -independent (nitroglycerin) agonists in saline-treated rats and rats chronically treated with nicotine (2 mg.kg(-1).day(-1) for 2 wk via an osmotic minipump). We found that NOS-dependent, but not -independent, vasodilatation was impaired in nicotine-treated compared with saline-treated rats. In addition, the production of superoxide anion (lucigenin chemiluminescence) was increased in rats treated with nicotine compared with saline-treated rats. Furthermore, using Western blot analysis, we found that chronic exposure to nicotine increased p47phox protein in the parietal cortex. Finally, we found that apocynin (40 mg.kg(-1).day(-1)) in the drinking water to inhibit NADPH oxidase alleviated impaired NOS-dependent cerebral vasodilatation in nicotine treated rats but did not alter NOS-dependent responses in saline treated rats and did not alter NOS-independent reactivity in saline- or nicotine-treated rats. These findings suggest that chronic exposure to nicotine impairs NOS-dependent dilatation of pial arterioles by a mechanism that appears to be related to the formation of superoxide anion via activation of NADPH oxidase.
Fang
Qin
Q
Dept. of Cellular and Integrative Physiology, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.
Sun
Hong
H
Arrick
Denise M
DM
Mayhan
William G
WG
D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015918:Infusion Pumps, Implantable; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology; D010841:Pia Mater / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D000098:Acetophenones; D004791:Enzyme Inhibitors; D018722:Nicotinic Agonists; D014665:Vasodilator Agents; D013481:Superoxides; D009538:Nicotine; C056165:acetovanillone; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D000109:Acetylcholine