Alcohol-induced impairment of neuronal nitric oxide synthase (nNOS)-dependent dilation of cerebral arterioles: Role of NAD(P)H oxidase

Hong Sun, Elizabeth Molacek, Hong Zheng, Qin Fang, Kaushik P. Patel, William G. Mayhan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The goal of the present study was to determine the role of NAD(P)H oxidase in alcohol consumption-induced impairment of nNOS-dependent reactivity in cerebral arterioles. Sprague-Dawley rats were fed an alcohol diet for 2-3 months. We measured the effects of acute (1 hour) and chronic (1 month) treatment with a NAD(P)H oxidase inhibitor, apocynin, on responses of parietal pial arterioles to nNOS-dependent agonists (NMDA and kainate) and an nitric oxide synthase (NOS)-independent agonist (nitroglycerin). In addition, we measured the expression of NAD(P)H oxidase subunits and superoxide production in parietal cortex. Topical application of NMDA and kainate produced dose-related dilation of pial arterioles. However, the magnitude of vasodilation to these agonists was significantly less in alcohol-fed rats. Treatment with apocynin (acute and chronic) did not alter vasodilation in nonalcohol-fed rats, but significantly improved vasodilation in alcohol-fed rats. Response of pial arterioles to nitroglycerin was similar in nonalcohol-fed and alcohol-fed rats, and was not affected by apocynin. In addition, we found an up-regulation of gp91phox and p47phox in parietal cortex of alcohol-fed rats. Finally, alcohol consumption produced an increase in superoxide production under basal conditions and in the presence of NADPH. Acute treatment with apocynin suppressed alcohol consumption-induced superoxide generation. Our findings suggest that NAD(P)H oxidase plays an important role in chronic alcohol consumption-induced impairment of nNOS-dependent dilation of cerebral arterioles.

Original languageEnglish (US)
Pages (from-to)321-328
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Arteries
  • Microcirculation
  • NAD(P)H oxidase
  • Nitric oxide
  • Oxygen radicals

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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