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(Stroke. 2006;37:495.)
© 2006 American Heart Association, Inc.

Original Contributions

Role of NAD(P)H Oxidase in Alcohol-Induced Impairment of Endothelial Nitric Oxide Synthase–Dependent Dilation of Cerebral Arterioles

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

From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha.

Correspondence to Hong Sun, MD, PhD, Department of Cellular and Integrative Physiology, 985850 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5850. E-mail hsu1{at}unmc.edu

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.

Key Words: alcohol • NADPH oxidase • nitric-oxide synthase • stroke