title: Temporal effect of alcohol consumption on reactivity of pial arterioles: role of oxygen radicals.
abstract: Chronic alcohol consumption reduces nitric oxide synthase-dependent responses of pial arterioles via mechanisms that remain uncertain. In addition, the temporal effects of alcohol on pial arterioles is unclear. Thus our goals were to examine the role of oxygen-derived free radicals in alcohol-induced impairment of cerebrovascular reactivity and the temporal effect of alcohol on reactivity of pial arterioles. Sprague-Dawley rats were pair-fed a liquid diet with or without alcohol for 2-3 wk, 2-3 mo, or 5-6 mo. We measured the in vivo diameter of pial arterioles in response to nitric oxide synthase-dependent dilators acetylcholine and ADP and the nitric oxide synthase-independent dilator nitroglycerin. In nonalcohol-fed rats, acetylcholine (1.0 and 10 microM) and ADP (10 and 100 microM) produced dose-related dilatation of pial arterioles. Whereas there was no difference in reactivity of arterioles to the agonists in rats fed the nonalcohol and alcohol diets for a period of 2-3 wk, there was a significant impairment in reactivity of arterioles to acetylcholine and ADP, but not nitroglycerin, in rats fed the alcohol diet for longer durations. We then found that treatment with superoxide dismutase did not alter baseline diameter of pial arterioles in nonalcohol-fed or alcohol-fed rats, but significantly improved impaired nitric oxide synthase-dependent dilatation of pial arterioles in alcohol-fed rats. Thus our findings suggest a temporal relationship in the effects of alcohol on reactivity of pial arterioles and that impaired nitric oxide synthase-dependent cerebral vasodilatation during chronic alcohol consumption may be related, in part, to enhanced release of oxygen-derived free radicals.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001160:Arterioles / Q000201:enzymology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D013481:Superoxides; D000431:Ethanol; D000244:Adenosine Diphosphate; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D000109:Acetylcholine