This Article Full Text Full Text (PDF) All Versions of this Article: 114/3/226    most recent CIRCULATIONAHA.105.596494v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheng, C.-P. Articles by Little, W. C. Search for Related Content PubMed PubMed Citation Articles by Cheng, C.-P. Articles by Little, W. C. Pubmed/NCBI databases Medline Plus Health Information Cardiomyopathy Related Collections Other heart failure Animal models of human disease Myocardial cardiomyopathy disease Related Article

(Circulation. 2006;114:226-236.)
© 2006 American Heart Association, Inc.

Heart Failure

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; 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.

Reprint requests to Che-Ping Cheng, MD, PhD, Cardiology Section, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045. E-mail ccheng{at}wfubmc.edu

Received October 20, 2005; revision received April 20, 2006; accepted May 12, 2006.

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.

---

 

CLINICAL PERSPECTIVE

Related Article:

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

This article has been cited by other articles:

				I. Laonigro, M. Correale, M. Di Biase, and E. Altomare Alcohol abuse and heart failure Eur J Heart Fail, May 1, 2009; 11(5): 453 - 462. [Abstract] [Full Text] [PDF]