CHANGES IN CARDIAC SIGNAL-TRANSDUCTION SYSTEMS IN CHRONIC ETHANOL TREATMENT PRECEDING THE DEVELOPMENT OF ALCOHOLIC CARDIOMYOPATHY

Chronic alcohol consumption has been postulated as an important pathog enetic mechanism for the development of alcoholic cardiomyopathy. This form of chronic heart failure shares with Other forms of cardiomyopat hy the pronounced alterations of the adrenergic signal transduction sy stems. These alterations include a significant reduction of beta-adren ergic receptors and a reduced responsiveness of The adenylyl cyclase. Changes of other receptor systems such as alpha-adrenergic and muscari nic receptors have not been studied extensively so far. To address the question if changes of the adrenergic signal transduction systems may occur early in the development of alcoholic cardiomyopathy and if alp ha(1)-adrenergic receptors and muscarinic receptors may be subjected t o an altered expression even before severe impairment of the left vent ricular function becomes obvious, rats were chronically fed with an al cohol diet containing 35% of total calorie intake as ethanol. In cardi ac plasma membranes beta-adrenergic receptors, cv adrenergic receptors , muscarinic receptors and adenylyl cyclase activities were determined after 4 and 8 weeks of chronic alcohol treatment. After these periods of chronic alcohol diet no signs of overt heart failure such as pleur al effusion or increased lung wet weight as parameters for congestion were present. Body weight gain was comparable in the controls and unde r chronic alcohol treatment in these adolescent rats. Both after 4 and 8 weeks of chronic alcohol treatment the density of cardiac beta-adre nergic receptors remained unchanged and all adenylyl cyclase activitie s remained fully responsive. In contrast, after 8 weeks of alcohol tre atment the developmental increase of cardiac muscarinic receptors in t he adolescent rats was greatly impaired resulting in a significantly r educed expression of these receptors even before clinical signs of hea rt failure. In contrast the density of cardiac alpha(1)-adrenergic rec eptors were significantly reduced already after 4 weeks of chronic alc ohol treatment with an additional impairment of the developmental incr ease after 8 weeks of alcohol treatment. These data characterize for t he first time early changes of cardiac receptor system in chronic alco hol treatment which precede tile development of overt heart failure. T hese changes include alpha(1)-adrenergic and muscarinic receptors, but in contrast to severe heart failure, leave the beta(1)-adrenergic sys tem and the responsiveness of the adenylyl cyclase intact. Additionall y these data show the developmentally increased expression of cardiac alpha(1)-adrenergic and muscarinic receptors in rat heart.