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 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.
Strasser
R H
RH
University of Heidelberg, Department of Cardiology, Pulmology and Angiology.
Nüchter
I
I
Rauch
B
B
Marquetant
R
R
Seitz
H
H
D000262:Adenylyl Cyclases / Q000097:blood; D000437:Alcoholism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D000262:Adenylyl Cyclases