Kuizinga M C, Smits J F, Arends J W
Department of Pathology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, The Netherlands.
J Mol Cell Cardiol. 1998 Feb;30(2):425-34. doi: 10.1006/jmcc.1997.0607.
The objective of the study was to investigate the involvement of angiotensin II receptor subtypes 1 and 2 in total interstitial cell and endothelial cell DNA synthesis and cardiac function after myocardial infarction (MI) in the rat. Rats with a MI were treated with either AT1 receptor antagonist GR138950C (2 mg/kg/day) or the AT2 receptor antagonist PD123319 (3 mg/kg/day). Total interstitial cell (that is endothelial cells and fibroblast-like cells) DNA synthesis in the interventricular septum was significantly increased 2 weeks after MI. 33+/-3% of DNA synthesizing cells were identified as endothelial cells. PD123319, but not GR138950C significantly reduced total interstitial DNA synthesis. Both agents did not alter the fraction of DNA synthesizing endothelial cells. The effects on cardiac function were studied in parallel groups. MI reduced both cardiac output and stroke volume at 3 weeks after MI PD123319 reduced CO, whereas GR138950C did not affect cardiac function. Thus, the data show that AT2 receptor blockade, but not AT1 receptor blockade early after rat myocardial infarction inhibits interstitial DNA synthesis and decreases cardiac function.
本研究的目的是探讨血管紧张素II 1型和2型受体在大鼠心肌梗死（MI）后总间质细胞和内皮细胞DNA合成及心脏功能中的作用。MI大鼠分别用AT1受体拮抗剂GR138950C（2毫克/千克/天）或AT2受体拮抗剂PD123319（3毫克/千克/天）进行治疗。MI后2周，室间隔中总间质细胞（即内皮细胞和成纤维样细胞）DNA合成显著增加。33±3%的DNA合成细胞被鉴定为内皮细胞。PD123319可显著降低总间质DNA合成，而GR138950C则无此作用。两种药物均未改变DNA合成内皮细胞的比例。在平行组中研究了对心脏功能的影响。MI后3周，MI降低了心输出量和每搏输出量，PD123319降低了心输出量，而GR138950C对心脏功能无影响。因此，数据表明，大鼠心肌梗死后早期，阻断AT2受体而非AT1受体可抑制间质DNA合成并降低心脏功能。
