Liu Y, Leri A, Li B, Wang X, Cheng W, Kajstura J, Anversa P
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Circ Res. 1998 Jun 15;82(11):1145-59. doi: 10.1161/01.res.82.11.1145.
To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volume at isolation. In both groups of myocytes, the AT1 receptor blocker losartan completely inhibited the consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte growth through the activation of AT1 receptors, which modulate the time and magnitude of this cellular response.
为了确定体外血管紧张素II(Ang II)刺激成年心室肌细胞是否会导致细胞肥大,通过共聚焦显微镜检查了肌细胞体积和每个细胞蛋白质含量的变化。此外,还考虑了梗死心肌细胞上Ang II受体上调可能增强和/或加速Ang II介导的心肌细胞生长的可能性。从梗死3天后的对照心脏和衰竭心脏中分离出的左心室肌细胞在Ang II存在下培养3天和7天。正常肌细胞在3天时体积和蛋白质含量没有增加,但在7天时这些参数分别增加了16%和20%。梗死心脏的肌细胞生长更快且更显著。在这些细胞中,给予Ang II后3天,肌细胞体积增加23%,蛋白质含量增加28%。尽管梗死心脏的肌细胞在分离时体积大19%,但其肥大反应更高。在两组肌细胞中,AT1受体阻滞剂氯沙坦完全抑制了Ang II的作用。相反,AT2受体拮抗剂PD123319对Ang II诱导的肥大没有影响。总之,Ang II通过激活AT1受体促进心肌细胞生长,AT1受体调节这种细胞反应的时间和幅度。