Figueredo V M, Chang K C, Baker A J, Camacho S A
Department of Medicine (Cardiology), San Francisco General Hospital, San Francisco, California 94110, USA.
Am J Physiol. 1998 Jul;275(1):H122-30. doi: 10.1152/ajpheart.1998.275.1.H122.
Long-standing heavy alcohol consumption acts as a chronic stress on the heart. It is thought that alcohol-induced changes of contractility are due to altered Ca2+ handling, but no measurements of cytosolic Ca2+ ([Ca2+]c) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced changes in contractility are due to altered Ca2+ handling by measuring [Ca2+]c (indo 1) in hearts from rats drinking 36% ethanol for 7 mo and age-matched controls. Peak left ventricular pressure was depressed (-16%), whereas rates of contraction (12%) and relaxation (14-20%) were faster in alcohol-exposed hearts. Systolic [Ca2+]c (808 +/- 45 vs. 813 +/- 45 nM), diastolic [Ca2+]c (195 +/- 11 vs. 193 +/- 10 nM), and rates of [Ca2+]c rise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca2+-handling proteins, sarcoplasmic reticulum Ca2+-ATPase and phospholamban, were the same in myocytes isolated from alcohol-exposed and control hearts (SDS-polyacrylamide gel). These data suggest that chronic alcohol-induced contractile changes are not due to altered Ca2+ handling but may be due to changes at the level of the myofilament. As a first step in elucidating the mechanism(s) of alcohol-induced changes at the myofilament, we assessed myosin heavy chain (MHC) isoform content (SDS-polyacrylamide gel). alpha-MHC was decreased relative to beta-MHC (a/a + b = 0.55 +/- 0.03 vs. 0.66 +/- 0.02; P < 0.02) in alcohol-exposed hearts, which cannot account for the observed alcohol-induced contractile changes. In conclusion, changes of myocardial contractility due to chronic alcohol exposure do not result from altered Ca2+ handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.
长期大量饮酒对心脏构成慢性应激。据认为，酒精引起的收缩性变化是由于钙处理改变所致，但长期酒精暴露后尚未对胞质钙（[Ca2+]c）进行测量。因此，进行了实验，通过测量饮用36%乙醇7个月的大鼠心脏和年龄匹配对照大鼠心脏中的[Ca2+]c（indo 1），来确定酒精引起的收缩性变化是否归因于钙处理的改变。酒精暴露组心脏的左心室峰值压力降低（-16%），而收缩速率（12%）和舒张速率（14 - 20%）更快。酒精暴露组和对照组心脏的收缩期[Ca2+]c（808±45对813±45 nM）、舒张期[Ca2+]c（195±11对193±10 nM）以及[Ca2+]c升高和下降速率相同。从酒精暴露组和对照组心脏分离的心肌细胞中，钙处理蛋白、肌浆网钙ATP酶和受磷蛋白的蛋白水平相同（SDS - 聚丙烯酰胺凝胶）。这些数据表明，慢性酒精诱导的收缩性变化并非由于钙处理改变，而可能是由于肌丝水平的变化。作为阐明酒精在肌丝水平诱导变化机制的第一步，我们评估了肌球蛋白重链（MHC）同工型含量（SDS - 聚丙烯酰胺凝胶）。在酒精暴露组心脏中，α - MHC相对于β - MHC减少（a/a + b = 0.55±0.03对0.66±0.02；P < 0.02），这无法解释观察到的酒精诱导的收缩性变化。总之，慢性酒精暴露引起的心肌收缩性变化并非由钙处理改变导致，而是由肌丝水平不涉及MHC同工型转变的变化引起。
