title: 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 (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.
authors.affiliation: Cardiology Section, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045, USA. ccheng@wfubmc.edu
authors.forename: Che-Ping
authors.initials: CP
authors.lastname: Cheng
authors.forename: Heng-Jie
authors.initials: HJ
authors.lastname: Cheng
authors.forename: Carol
authors.initials: C
authors.lastname: Cunningham
authors.forename: Zakariya K
authors.initials: ZK
authors.lastname: Shihabi
authors.forename: David C
authors.initials: DC
authors.lastname: Sane
authors.forename: Thomas
authors.initials: T
authors.lastname: Wannenburg
authors.forename: William C
authors.initials: WC
authors.lastname: Little
mesh_terms: 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
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers