Role of NAD(P)H oxidase in alcohol-induced impairment of endothelial nitric oxide synthase-dependent dilation of cerebral arterioles

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

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background and Purpose - Our goal was to determine whether NAD(P)H oxidase is involved in impaired endothelial nitric oxide synthase (eNOS)-dependent reactivity of cerebral arterioles during chronic alcohol consumption. Methods - Sprague-Dawley rats were fed with an alcohol diet for 2 to 3 months. We determined the effects of acute and chronic treatment with an NAD(P)H oxidase inhibitor, apocynin, on responses of pial arterioles to eNOS-dependent agonists (acetylcholine and ADP) and an eNOS-independent agonist (nitroglycerin). Expression of NAD(P)H oxidase in pial arterioles was measured with the use of real-time polymerase chain reaction and Western blot analysis, and superoxide production was measured with the use of lucigenin-enhanced chemiluminescence. Results - Vasodilation in response to acetylcholine and ADP, but not nitroglycerin, was significantly less in alcohol-fed rats. Treatment with apocynin did not alter vasodilation in non-alcohol-fed rats but significantly improved impaired vasodilation in alcohol-fed rats. In addition, an upregulation of p47phox in pial arterioles was found in alcohol-fed rats. Furthermore, alcohol consumption increased superoxide production under basal conditions and in the presence of ADP and NAD(P)H. Conclusions - Our findings suggest that NAD(P)H oxidase plays a role in chronic alcohol consumption-induced impairment of eNOS-dependent dilation of cerebral arterioles.

Original languageEnglish (US)
Pages (from-to)495-500
Number of pages6
JournalStroke
Volume37
Issue number2
DOIs
Publication statusPublished - Feb 1 2006

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Keywords

  • Alcohol
  • NADPH oxidase
  • Nitric-oxide synthase
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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