Alcohol-induced impairment of neuronal nitric oxide synthase (nNOS)-dependent dilation of cerebral arterioles: role of NAD(P)H oxidase.
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.
Sun
Hong
H
Department of Cellular and Integrative Physiology, 985850 University of Nebraska Medical Center, Omaha, NE 68198-5850, USA. hsu1@unmc.edu
Molacek
Elizabeth
E
Zheng
Hong
H
Fang
Qin
Q
Patel
Kaushik P
KP
Mayhan
William G
WG
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D013687:Telencephalon / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D014664:Vasodilation / Q000187:drug effects*
D000098:Acetophenones; D000975:Antioxidants; D013481:Superoxides; D000431:Ethanol; C056165:acetovanillone; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases