Published Online
on July 10, 2006

A more recent version of this article appeared on July 18, 2006

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Submitted on October 20, 2005
Revised on April 20, 2006
Accepted on May 12, 2006

Angiotensin II Type 1 Receptor Blockade Prevents Alcoholic Cardiomyopathy

Che-Ping Cheng MD, PhD^*, Heng-Jie Cheng MD, PhD, Carol Cunningham PhD, Zakariya K. Shihabi PhD, David C. Sane MD, Thomas Wannenburg MD, and William C. Little MD

From the Cardiology Section, Department of Internal Medicine (C.-P.C., H.-J.C., D.C.S., T.W., W.C.L.), Department of Biochemistry (C.C.), and Department of Pathology (Z.K.S.), Wake Forest University School of Medicine, Winston-Salem, NC.

^* To whom correspondence should be addressed. E-mail: ccheng{at}wfubmc.edu.

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 (AT₁) 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 µm/s) and relengthening; and decreased peak systolic Ca²⁺ transient ([Ca²⁺]_iT) and L-type Ca²⁺ current (I_Ca,L; P<0.05). Irbesartan prevented the alcohol-induced decreases in LV and myocyte contraction, relaxation, peak [Ca²⁺]_iT, and I_Ca,L. With alcohol plus irbesartan, plasma Ang II, cardiac angiotensin-converting enzyme activity, and AT₁ remained close to control values.

Conclusions--Chronic alcohol consumption produces RAS activation followed by progressive cardiac dysfunction. The cardiac dysfunction is prevented by AT₁ receptor blockade.

Key words: angiotensin • alcohol • hemodynamics • myocytes • contractility

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Circulation 2006 114: 183. [Extract] [Full Text]

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