Chronic Ethanol Administration Prevents Compensatory Cardiac Hypertrophy in Pressure Overload

BACKGROUND Alcohol is among the most commonly abused drugs worldwide and affects many organ systems, including the heart. Alcoholic cardiomyopathy is characterized by a dilated cardiac phenotype with extensive hypertrophy and extracellular matrix (ECM) remodeling. We have previously shown that chronic ethanol administration accelerates the progression to heart failure in a rat model of volume overload. However, the mechanism by which this decompensation occurs is unknown. For this study, we hypothesized that chronic ethanol administration would prevent compensatory hypertrophy and cardiac remodeling in a rodent model of pressure overload (PO). METHODS Abdominal aortic constriction was used to create PO in 8 week old male Wistar rats. Alcohol administration was performed via chronic intermittent ethanol vapor inhalation for 2 weeks prior to surgery and for the duration of the 8 week study. Echocardiography measurements were taken to assess ventricular functional and structural changes. RESULTS Pressure overload increased posterior wall thickness and the hypertrophic markers, atrial and B-type natriuretic peptides (ANP and BNP). With the added stressor of ethanol, wall thickness, ANP, and BNP decreased in PO animals. The combination of PO and ethanol resulted in increased wall stress compared to PO alone. PO also caused increased expression of collagen I and III, whereas ethanol alone only increased collagen III. The combined stresses of PO and ethanol led to an increase in collagen I expression, but collagen III did not change, resulting in an increased collagen I/III ratio in the PO rats treated with ethanol. Lastly, Notch1 expression was significantly increased only in the PO rats treated with ethanol. CONCLUSIONS Our data indicate that chronic ethanol may limit the cardiac hypertrophy induced by PO that may be associated with a Notch1 mechanism, resulting in increased wall stress and altered ECM profile. This article is protected by copyright. All rights reserved.