EFFECT OF CHRONIC ALCOHOL-CONSUMPTION ON RESPONSES OF CEREBRAL ARTERIOLES

The goal of this study was to determine whether chronic ingestion of a lcohol alters dilatation of cerebral arterioles in response to agonist s that produce activation of adenylate cyclase and activation of ATP-s ensitive potassium channels. Rats were fed liquid diets with or withou t ethanol for 2 to 2.5 months. In vivo diameter of pial arterioles was measured in alcohol-fed and nonalcohol-fed rats during superfusion wi th 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 impa ired in alcohol-fed rats. Isoproterenol (1.0 mu M) dilated cerebral ar terioles by 15 +/- 3% in nonalcohol-fed rats, but by only 7 +/- 2% in alcohol-fed rats. In contrast, dilatation of pial arterioles in respon se to forskolin was similar in nonalcohol-fed and alcohol-fed rats. Di latation of pial arterioles in response to activation of ATP-sensitive potassium channels was impaired in alcohol-fed compared with nonalcoh ol-fed rats. Cromakalim (1.0 mu M) 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 nit roglycerin was similar in alcohol and nonalcohol-fed rats. The finding s 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 sug gest that impaired vasodilator mechanisms during chronic alcohol consu mption may have important implications for the pathogenesis of cerebro vascular abnormalities observed during chronic alcoholism.