Chronic ethanol enhances adenosine antiadrenergic actions in the isolated rat heart.
BACKGROUND
Chronic alcohol consumption elicits an increase in catecholamine release, which may be detrimental to heart function. Adenosine attenuates adrenergic stimulation via an adenosine receptor-mediated antiadrenergic action. This study investigated the effect of ethanol on adenosine antiadrenergic actions and adenosine release in the rat heart.


METHODS
Rats were pair-fed a liquid diet with or without ethanol for 4 weeks or 8 months. Hearts were isolated for determination of contractile function, and coronary effluents were collected for adenosine content. Dose-response relationships for phenylisopropyladenosine (PIA) were determined for hearts adrenergically stimulated by isoproterenol. Experiments were also conducted with normal hearts with or without ethanol (25 mM) administered acutely. The effect of PIA on adenylyl cyclase activities of adrenergic-stimulated crude membrane preparations obtained from alcoholic and nonalcoholic hearts 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 similar with or without adrenergic stimulation. PIA 50% inhibiting concentration (IC50) values for contractile function were reduced from pair-fed control values. Acute ethanol did not significantly change the PIA IC50 value. Chronic 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 concentration. Therefore, adenosine-induced cardioprotection against increased catecholamine stimulation is enhanced by ethanol.
Fenton
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Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. richard.fenton@umassmed.edu
Chung
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D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004357:Drug Synergism; D004452:Echocardiography; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D011687:Purines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018674:Adrenergic Antagonists; D002317:Cardiovascular Agents; D002492:Central Nervous System Depressants; D011687:Purines; D000431:Ethanol; D007288:Inosine; D000262:Adenylyl Cyclases; D000241:Adenosine