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 (AT1) blockade on the development of alcoholic cardiomyopathy.


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 microm/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.
Cheng
Che-Ping
CP
Cardiology Section, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045, USA. ccheng@wfubmc.edu
Cheng
Heng-Jie
HJ
Cunningham
Carol
C
Shihabi
Zakariya K
ZK
Sane
David C
DC
Wannenburg
Thomas
T
Little
William C
WC
D000437:Alcoholism / Q000150:complications; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D032342:Muscle Cells / Q000473:pathology; D009206:Myocardium / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers