Kabour A, Henegar J R, Janicki J S
Department of Internal Medicine, University of Missouri, Columbia 65212.
J Cardiovasc Pharmacol. 1994 Apr;23(4):547-53. doi: 10.1097/00005344-199404000-00005.
Pathophysiologic levels of angiotensin II (AII) produce myocyte necrosis. We investigated whether the cardiotoxic effects of AII are mediated through the AII type I receptor (AT1). Seven groups (4-6 rats/group) were given AII (150 ng/min) alone or in combination with the AT1 antagonist losartan (7.5 mg/day). Groups were as follows: A1, A4, and L1 received AII for 2 days; A2 and L2 received AII for 9 days; and A3 and L3 received AII for 2 days and again for 2 days 5 days later. Groups L1, L2, and L3 also received losartan 2 days before and throughout the AII infusion period. All rats except those in group A4 were killed at the end of their respective infusion periods (group A4 rats were killed 7 days after infusion). Group A1 had multifocal areas of recent myocyte injury. Groups A2 and A4 had multifocal scars and only a few new areas of myocyte damage. Group A3, in addition to scar formation, had de novo areas of necrosis. There was no evidence of myocyte necrosis in groups L1, L2, and L3. Thus, AII-related myocyte necrosis is receptor mediated. Moreover, a chronic increase in AII appears to cause cardioprotective downregulation of the AT1 receptor.
血管紧张素II（AII）的病理生理水平会导致心肌细胞坏死。我们研究了AII的心脏毒性作用是否通过I型血管紧张素II受体（AT1）介导。将七组（每组4 - 6只大鼠）单独给予AII（150纳克/分钟）或与AT1拮抗剂氯沙坦（7.5毫克/天）联合使用。分组如下：A1、A4和L1接受AII治疗2天；A2和L2接受AII治疗9天；A3和L3接受AII治疗2天，5天后再治疗2天。L1、L2和L3组在AII输注期开始前2天及整个输注期也接受氯沙坦治疗。除A4组大鼠外，所有大鼠在各自输注期结束时处死（A4组大鼠在输注后7天处死）。A1组有多处近期心肌细胞损伤区域。A2组和A4组有多处瘢痕，仅有少数新的心肌细胞损伤区域。A3组除瘢痕形成外，还有新出现的坏死区域。L1、L2和L3组没有心肌细胞坏死的证据。因此，AII相关的心肌细胞坏死是由受体介导的。此外，AII的慢性增加似乎会导致AT1受体的心脏保护下调。
