Inhibition of NADPH oxidase improves impaired reactivity of pial arterioles during chronic exposure to nicotine

Qin Fang, Hong Sun, Denise M. Arrick, William G. Mayhan

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)631-636
Number of pages6
JournalJournal of Applied Physiology
Issue number2
StatePublished - Feb 2006
Externally publishedYes


  • Apocynin
  • Brain
  • Nitric oxide
  • Smoking
  • Superoxide anion

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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