Lefroy D C, Wharton J, Crake T, Knock G A, Rutherford R A, Suzuki T, Morgan K, Polak J M, Poole-Wilson P A
Department of Histochemistry, Royal Postgraduate Medical School, London, UK.
J Mol Cell Cardiol. 1996 Feb;28(2):429-40. doi: 10.1006/jmcc.1996.0039.
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 125Iangiotensin II binding and quantitative autoradiography. The 125Iangiotensin 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 125Iangiotensin 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 125Iangiotensin II was antagonised by losartan, an AT1 receptor antagonist, but not by an AT2 receptor antagonist. Microautoradiography of 125I 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.
心肌梗死后血浆和心脏肾素 - 血管紧张素系统可能被激活。因此，心肌可能会暴露于浓度升高的血管紧张素II中，这可能会导致心肌损伤。本研究的目的是确定血管紧张素II在梗死心脏中的潜在作用位点。通过左冠状动脉结扎诱导大鼠心肌梗死，在18小时、7天或8个月后取出心脏进行研究。通过[125I]（Sar1，Ile8）血管紧张素II结合和定量放射自显影评估局部心室血管紧张素II受体密度。[125I]（Sar1，Ile8）血管紧张素II结合在18小时时未发生变化，但在左心室梗死区域7天时增加（73.2±3.2 amol/mm2，平均值±标准误），与非梗死区域（1.6±0.2 amol/mm2，P<0.0001）以及假手术对照动物的左心室心肌（1.3±0.1 amol/mm2，P<0.0001）相比。冠状动脉结扎8个月后，[125I]（Sar1，Ile8）血管紧张素II结合密度仍升高，但有所降低（49.0±5.7 amol/mm2，与对照组相比P<0.0001，与7天梗死组相比P = 0.0058）。[125I]（Sar1，Ile8）血管紧张素II结合增加可被AT1受体拮抗剂氯沙坦拮抗，但不能被AT2受体拮抗剂拮抗。[125I]（Sar1，Ile8）血管紧张素II的显微放射自显影以及使用苦味酸天狼星红染色和免疫染色评估胶原沉积表明，心肌梗死区域AT1受体密度的局部增加与成纤维细胞浸润和胶原沉积有关。梗死瘢痕及其内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。
