Angiotensin II type 1 receptor blockade prevents alcoholic cardiomyopathy

Background - Activation of the renin-angiotensin system (RAS) may contribute to the development of alcoholic cardiomyopathy. We evaluated the effect of angiotensin II (Ang II) type 1 receptor (AT(1)) blockade on the development of alcoholic cardiomyopathy. Methods and Results - We serially evaluated left ventricular (LV) and cardiomyocyte function and the RAS over 6 months in 3 groups of instrumented dogs. Eight animals received alcohol (once per day orally, providing 33% of total daily caloric intake); 6 received alcohol and irbesartan (5 mg (.) kg(-1) (.) d(-1) PO); and 8 were controls. Compared with controls, alcohol ingestion caused sustained RAS activation with progressive increases in plasma levels of Ang II, renin activity, LV angiotensin-converting enzyme activity, and LV myocyte Ang II AT1 receptor expression. The RAS activation was followed by a progressive fall in LV contractility (E-ES, alcohol-fed dogs 3.9 +/- 0.8 versus control dogs 8.1 +/- 1.0 mm Hg/mL); reductions in the peak velocity of myocyte shortening (78.9 +/- 5.1 versus 153.9 +/- 6.2 mu m/s) and relengthening; and decreased peak systolic Ca2+ transient ([Ca2+](iT)) and L-type Ca2+ current (I-Ca,I-L; P < 0.05). Irbesartan prevented the alcohol-induced decreases in LV and myocyte contraction, relaxation, peak [Ca2+](iT), and I-Ca,I-L. With alcohol plus irbesartan, plasma Ang II, cardiac angiotensin-converting enzyme activity, and AT(1) remained close to control values. Conclusions - Chronic alcohol consumption produces RAS activation followed by progressive cardiac dysfunction. The cardiac dysfunction is prevented by AT(1) receptor blockade.