Chronic ethanol enhances adenosine antiadrenergic actions in the isolated rat heart

Background: Chronic alcohol consumption elicits an increase in catecholamin e release, which may be detrimental to heart function. Adenosine attenuates adrenergic stimulation via an adenosine receptor-mediated antiadrenergic a ction. This study investigated the effect of ethanol on adenosine antiadren ergic actions and adenosine release in the rat heart. Methods: Rats were pair-fed a liquid diet with or without ethanol for 4 wee ks or 8 months. Hearts were isolated for determination of contractile funct ion, and coronary effluents were collected for adenosine content. Dose-resp onse relationships for phenylisopropyladenosine (PIA) were determined for h earts adrenergically stimulated by isoproterenol. Experiments were also con ducted with normal hearts with or without ethanol (25 mM) administered acut ely. The effect of PIA on adenylyl cyclase activities of adrenergic-stimula ted crude membrane preparations obtained from alcoholic and nonalcoholic he arts was determined. Results: Acute ethanol reduced basal adenosine release: by 39%, but it did not significantly decrease adenosine release during adrenergic stimulation. In hearts chronically treated with ethanol for 4 weeks, adenosine release values before and during adrenergic stimulation were significantly reduced from control values. After 8 months of ethanol, adenosine release was simil ar with or without adrenergic stimulation. PIA50% inhibiting concentration (IC50) values for contractile function were reduced from pair-fed control v alues. Acute ethanol did not significantly change the PIA IC(50)value. Chro nic ethanol reduced the PIA IC50 for adenylyl cyclase by 96%. Conclusions: Chronic ethanol treatment increases the antiadrenergic action of adenosine by mechanisms that seem independent of changes in adenosine co ncentration. Therefore, adenosine-induced cardioprotection against increase d catecholamine stimulation is enhanced by ethanol.