Regional changes in angiotensin II receptor density after experimental myocardial infarction.
Regional changes in angiotensin II receptor density after experimental myocardial infarction.
复制标题
实验性心肌梗死后血管紧张素 II 受体密度的区域变化。
DOI：
10.1006/jmcc.1996.0039
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发表时间：
1996
影响因子：
5
通讯作者：
P. Poole‐Wilson
中科院分区：
文献类型：
--
作者：
D. Lefroy;J. Wharton;T. Crake;G. Knock;R. A. Rutherford;Tak Suzuki;Kevin Morgan;Julia M. Polak;P. Poole‐Wilson
心肌梗死后血浆和心脏的肾素-血管紧张素系统可能被激活。因此，心肌可能暴露于浓度增加的血管紧张素II，这可能导致心肌损伤。本研究的目的是确定血管紧张素II在梗死心脏的潜在作用部位。通过左冠状动脉结扎诱导大鼠心肌梗死，并在18小时、7天或8个月后取出心脏进行研究。局部心室血管紧张素II受体密度通过[125 I]（Sar 1，Ile 8）血管紧张素II结合和定量放射自显影来评估。[125 I]（Sar 1，Ile 8）血管紧张素II结合在18 h时无变化，但在7天时在左心室梗死区增加（73.2 +/- 3.2阿莫尔/mm 2，平均值+/- S.E.M.）与非梗死区（1.6 +/- 0.2阿莫尔/mm 2，P < 0.0001）和假手术对照动物的左心室心肌（1.3 +/- 0.1阿莫尔/mm 2，P < 0.0001）相比。冠脉结扎后8个月，[125 I]（Sar 1，Ile 8）血管紧张素II结合密度仍然增加，但减少（49.0 +/- 5.7阿莫尔/mm 2，P < 0.0001 vs对照组，P = 0.0058 vs 7天梗死组）。[125 I]（Sar 1，Ile 8）血管紧张素II的结合增加被氯沙坦（一种AT 1受体拮抗剂）拮抗，但不被AT 2受体拮抗剂拮抗。[125 I]（Sar 1，Ile 8）血管紧张素II的显微放射自显影，以及使用天狼星苦染色和免疫染色评估胶原沉积表明，心肌梗死区域AT 1受体密度的区域性增加与成纤维细胞浸润和胶原沉积相关。梗死瘢痕和其中的心脏成纤维细胞表达高水平的血管紧张素II受体，因此代表心肌梗死后血管紧张素II作用的潜在靶点。
The plasma and cardiac renin-angiotensin systems may be activated after myocardial infarction. The myocardium may therefore be exposed to increased concentrations of angiotension II, which may contribute to myocardial injury. The purpose of this study was to identify the potential sites of action of angiotensin II in the infarcted heart. Myocardial infarction was induced in rats by left coronary artery ligation, and the hearts were removed for study after 18 h, 7 days, or 8 months. The regional ventricular angiotensin II receptor density was assessed by [125I](Sar1,Ile8)angiotensin II binding and quantitative autoradiography. The [125I](Sar1,Ile8)angiotensin II binding was unchanged at 18 h, but was increased at 7 days in the infarcted region of the left ventricle (73.2 +/- 3.2 amol/mm2, mean +/- S.E.M.) compared with the non-infarcted region (1.6 +/- 0.2 amol/mm2, P < 0.0001) and with the left ventricular myocardium of sham-operated control animals (1.3 +/- 0.1 amol/mm2, P < 0.0001). The increased [125I](Sar1,Ile8)angiotensin II binding density was still present, but diminished, at 8 months after coronary ligation (49.0 +/- 5.7 amol/mm2, P < 0.0001 v control, P = 0.0058 v 7-day infarcts). The increased binding of [125I](Sar1,Ile8)angiotensin II was antagonised by losartan, an AT1 receptor antagonist, but not by an AT2 receptor antagonist. Microautoradiography of [125I](Sar1,Ile8) angiotensin II, and assessment of collagen deposition using picrosirius staining and immunostaining demonstrated that the regional increase in AT1 receptor density in the infarcted region of myocardium was associated with fibroblast infiltration and collagen deposition. The infarct scar and the cardiac fibroblasts within it express high levels of angiotension II receptors and therefore represent potential targets for the actions of angiotensin II after myocardial infarction.