Using an animal model of alcoholism, we investigated whether 4 months of ethanol consumption was associated with a preclinical stage of alcoholic cardiomyopathy (ACM), as well as activation of the renin-angiotensin system and natriuretic peptides (NPs). In other forms of cardiovascular disease, the latter peptide systems have been used as markers of left ventricular (LV) remodeling and dysfunction. Rats were fed either a liquid ethanol or control diet, and serial blood samples were collected at baseline, as well as at 2 and 4 months, for plasma renin activity (PRA), angiotensin II (ANG II), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) levels. Serial echocardiography (echo) was performed at the same time points, and isolated heart studies were performed to assess ex vivo contractility at 4 months. In both groups at 4 months, there were significant and similar increases in end-diastolic and end-systolic echo dimensions and LV mass. At 4 months, however, a significant decrease was found in the relative wall thickness in the ethanol-fed group compared with findings for the control group. In both groups at 4 months, significant and similar time-dependent decreases were shown in BNP and ANP levels compared with baseline values. No differences were found in NP gene expression or tissue levels. In both groups at 4 months, significant and similar increases were found in ANG II levels compared with baseline values. Over time, in both groups, PRA levels were unchanged. In this study, the only cardiac structural feature characteristic of a preclinical ACM was a decrease in relative wall thickness. (C) 2003 Elsevier Science Inc. All rights reserved.