Angiotensin II type 1 receptor blockade prevents alcoholic cardiomyopathy
Angiotensin II type 1 receptor blockade prevents alcoholic cardiomyopathy
复制标题
DOI：
10.1161/circulationaha.105.596494
复制
发表时间：
2006-07-18
期刊：
影响因子：
37.8
通讯作者：
Little, William C.
中科院分区：
文献类型：
--
作者：
Cheng, Che-Ping;Cheng, Heng-Jie;Little, William C.
背景：肾素-血管紧张素系统（RAS）的激活可能促进酒精性心肌病的发生。我们评估了血管紧张素II（Ang II）1型受体（AT（1））阻断对酒精性cardiomyosis.Methods和Results发展的影响-我们连续评估了左心室（LV）和心肌细胞功能和RAS超过6个月的3组instrumented狗。8只动物接受酒精（每天一次口服，提供每日总热量摄入的33%）; 6只接受酒精和厄贝沙坦（5 mg（.）kg（-1）（.）d（-1）PO），对照组8例。与对照组相比，酒精摄入引起持续RAS激活，血浆Ang II水平、肾素活性、LV血管紧张素转换酶活性和LV心肌细胞Ang II AT 1受体表达逐渐增加。RAS激活后，LV收缩力逐渐下降（E-ES，酒精喂养犬3.9 ± 0.8 mmHg/mL，对照犬8.1 ± 1.0 mmHg/mL）;肌细胞缩短的峰值速度降低（78.9 +/- 5.1 vs 153.9 +/- 6.2 μ m/s）和再充盈;收缩期峰值钙瞬变（[Ca 2 +]（iT））和L型钙电流（I-Ca，I-L; P < 0.05）降低。厄贝沙坦可防止酒精引起的LV和心肌细胞收缩、舒张、[Ca 2 +]峰（iT）和I-Ca、I-L降低。酒精加厄贝沙坦，血浆血管紧张素II，心脏血管紧张素转换酶的活性，和AT（1）保持接近控制values.Conclusions -慢性酒精消费产生RAS激活，随后进行性心功能障碍。AT（1）受体阻滞剂可预防心功能不全。
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 (AT(1)) 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 mu m/s) and relengthening; and decreased peak systolic Ca2+ transient ([Ca2+](iT)) and L-type Ca2+ current (I-Ca,I-L; P < 0.05). Irbesartan prevented the alcohol-induced decreases in LV and myocyte contraction, relaxation, peak [Ca2+](iT), and I-Ca,I-L. With alcohol plus irbesartan, plasma Ang II, cardiac angiotensin-converting enzyme activity, and AT(1) remained close to control values.Conclusions - Chronic alcohol consumption produces RAS activation followed by progressive cardiac dysfunction. The cardiac dysfunction is prevented by AT(1) receptor blockade.