title: Effect of chronic alcohol consumption on responses of cerebral arterioles.
abstract: The goal of this study was to determine whether chronic ingestion of alcohol alters dilatation of cerebral arterioles in response to agonists that produce activation of adenylate cyclase and activation of ATP-sensitive potassium channels. Rats were fed liquid diets with or without ethanol for 2 to 2.5 months. In vivo diameter of pial arterioles was measured in alcohol-fed and nonalcohol-fed rats during superfusion with isoproterenol, forskolin, cromakalim, and nitroglycerin. Dilatation of pial arterioles in response to activation of adenylate cyclase via stimulation of beta-adrenergic receptors using isoproterenol was impaired in alcohol-fed rats. Isoproterenol (1.0 microM) dilated cerebral arterioles by 15 +/- 3% in nonalcohol-fed rats, but by only 7 +/- 2% in alcohol-fed rats. In contrast, dilatation of pial arterioles in response to forskolin was similar in nonalcohol-fed and alcohol-fed rats. Dilatation of pial arterioles in response to activation of ATP-sensitive potassium channels was impaired in alcohol-fed compared with nonalcohol-fed rats. Cromakalim (1.0 microM) dilated pial arterioles by 22 +/- 5% in nonalcohol-fed rats, but by only 5 +/- 2% in alcohol-fed rats (p < 0.05). In contrast, dilatation of pial arterioles in response to nitroglycerin was similar in alcohol and nonalcohol-fed rats. The findings of the present study suggest that chronic alcohol ingestion impairs dilatation of cerebral resistance arterioles in response to activation of adenylate cyclase via stimulation of beta-adrenergic receptors and in response to activation of ATP-sensitive potassium channels. We suggest that impaired vasodilator mechanisms during chronic alcohol consumption may have important implications for the pathogenesis of cerebrovascular abnormalities observed during chronic alcoholism.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
authors.forename: S P
authors.initials: SP
authors.lastname: Didion
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000098:blood supply*; D008297:Male; D010841:Pia Mater / Q000098:blood supply; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate