AT1 receptor blockade with irbesartan prevented alcohol-induced decreases in LV contractility (alcohol alone 3.9 vs control 8.1 mm Hg/mL) and myocyte function in a canine model.
Does irbesartan prevent cardiac dysfunction in a canine model of alcoholic cardiomyopathy?
AT1 receptor blockade with irbesartan prevents the development of alcoholic cardiomyopathy and progressive cardiac dysfunction in a canine model.
p-value: p=<0.05
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 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 et al. (2006) studied Alcoholic cardiomyopathy (n=22). Irbesartan vs. Alcohol alone and healthy controls was evaluated on Left ventricular (LV) and cardiomyocyte function (p=<0.05). AT1 receptor blockade with irbesartan prevented alcohol-induced decreases in LV contractility (alcohol alone 3.9 vs control 8.1 mm Hg/mL) and myocyte function in a canine model.