Angiotensin II Type 1 Receptor Blockade Prevents Alcoholic Cardiomyopathy

Abstract

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 AT 1 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 μm/s) and relengthening; and decreased peak systolic Ca 2+ transient ([Ca 2+ ] iT ) and L-type Ca 2+ current ( I Ca,L ; P <0.05). Irbesartan prevented the alcohol-induced decreases in LV and myocyte contraction, relaxation, peak [Ca 2+ ] iT , and I Ca,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.