Chronic alcohol consumption has been postulated as an important pathogenetic mechanism for the development of
alcoholic cardiomyopathy. This form of chronic
heart failure shares with other forms of
cardiomyopathy the pronounced alterations of the
adrenergic signal transduction systems. These alterations include a significant reduction of
beta-adrenergic receptors and a reduced responsiveness of the
adenylyl cyclase. Changes of other receptor systems such as alpha-
adrenergic and
muscarinic 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 alpha 1-adrenergic receptors and
muscarinic receptors may be subjected to an altered expression even before severe impairment of the left ventricular function becomes obvious, rats were chronically fed with an alcohol diet containing 35% of total calorie intake as
ethanol. In cardiac plasma membranes
beta-adrenergic receptors, alpha 1-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
pleural effusion or increased
lung wet weight as parameters for congestion were present.
Body weight gain was comparable in the controls and under chronic alcohol treatment in these adolescent rats. Both after 4 and 8 weeks of chronic alcohol treatment the density of cardiac
beta-adrenergic receptors remained unchanged and all
adenylyl cyclase activities remained fully responsive. In contrast, after 8 weeks of alcohol treatment the developmental increase of cardiac
muscarinic receptors in the adolescent rats was greatly impaired resulting in a significantly reduced expression of these receptors even before clinical signs of
heart failure. In contrast the density of cardiac alpha 1-adrenergic receptors were significantly reduced already after 4 weeks of chronic alcohol treatment with an additional impairment of the developmental increase after 8 weeks of alcohol treatment. These data characterize for the first time early changes of cardiac receptor system in chronic alcohol treatment which precede the development of overt
heart failure. These changes include alpha 1-adrenergic and
muscarinic receptors, but in contrast to severe
heart failure, leave the beta 1-adrenergic system and the responsiveness of the
adenylyl cyclase intact. Additionally these data show the developmentally increased expression of cardiac alpha 1-adrenergic and
muscarinic receptors in rat heart.