Temporal effect of alcohol consumption on reactivity of pial arterioles: role of oxygen radicals

Chronic alcohol consumption reduces nitric oxide synthase-dependent respons es of pial arterioles via mechanisms that remain uncertain. In addition, th e temporal effects of alcohol on pial arterioles is unclear. Thus our goals were to examine the role of oxygen-derived free radicals in alcohol-induce d impairment of cerebrovascular reactivity and the temporal effect of alcoh ol on reactivity of pial arterioles. Sprague-Dawley rats were pair-fed a li quid diet with or without alcohol for 2-3 wk, 2-3 mo, or 5-6 mo. We measure d the in vivo diameter of pial arterioles in response to nitric oxide synth ase-dependent dilators acetylcholine and ADP and the nitric oxide synthase- independent dilator nitroglycerin. In nonalcohol-fed rats, acetylcholine (1 .0 and 10 muM) and ADP (10 and 100 muM) produced dose-related dilatation of pial arterioles. Whereas there was no difference in reactivity of arteriol es to the agonists in rats fed the nonalcohol and alcohol diets for a perio d 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 d iet for longer durations. We then found that treatment with superoxide dism utase did not alter baseline diameter of pial arterioles in nonalcohol-fed or alcohol-fed rats, but significantly improved impaired nitric oxide synth ase-dependent dilatation of pial arterioles in alcohol-fed rats. Thus our f indings suggest a temporal relationship in the effects of alcohol on reacti vity of pial arterioles and that impaired nitric oxide synthase-dependent c erebral vasodilatation during chronic alcohol consumption may be related, i n part, to enhanced release of oxygen-derived free radicals.