Johansson Maria E, Wickman Anna, Fitzgerald Sharyn M, Gan Li-ming, Bergström Göran
Department of Physiology, Institute of Physiology and Pharmacology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
J Hypertens. 2005 Aug;23(8):1541-9. doi: 10.1097/01.hjh.0000174078.95745.77.
Angiotensin II (Ang II) accelerates atherogenesis in ApoE mice via the angiotensin II, type 1 receptor (AT1) while the type 2 receptor (AT2) is suggested to counteract atherogenesis. To confirm and further explore this possibility, we studied the effect of AT2 receptor antagonism on Ang II-accelerated atherosclerosis.
ApoE mice were fed a standard or high cholesterol diet (1.25%) for 4 weeks. Mice on each diet were treated with either Ang II (0.5 microg/kg per min) or Ang II in combination with PD123319 (3 mg/kg per day). Plaque distribution was assessed by en face quantification of the thoracic aorta and in cross-sections of the aortic root. Mean arterial pressure (MAP) was measured. AT1 and AT2 receptor expression were analysed using real-time polymerase chain reaction (PCR) and the localization of the AT2 receptor protein confirmed with immunohistochemistry.
Ang II infusion increased MAP only in mice on a standard diet (P < 0.001). Regardless of diet, Ang II-infused mice had 22-30 times increased plaque area in the thoracic aorta (P < 0.001 for both). Ang II had no effect on plaque in the aortic root. Plaque area was not affected by PD123319. AT2 receptor was heavily expressed in the plaques and increased six- to ninefold by a high cholesterol diet and Ang II infusion (P < 0.01).
Ang II increases the extent of atherosclerosis in ApoE mice. Despite up-regulation of the AT2 receptor, we found no support for an effect of the AT2 receptor on atherogenesis in this model.
血管紧张素II（Ang II）通过血管紧张素II 1型受体（AT1）加速载脂蛋白E（ApoE）小鼠的动脉粥样硬化形成，而2型受体（AT2）则被认为具有抗动脉粥样硬化作用。为证实并进一步探究这种可能性，我们研究了AT2受体拮抗作用对Ang II加速的动脉粥样硬化的影响。
给ApoE小鼠喂食标准或高胆固醇饮食（1.25%）4周。每种饮食组的小鼠分别接受Ang II（0.5微克/千克每分钟）或Ang II与PD123319（3毫克/千克每天）联合治疗。通过对胸主动脉进行整体定量分析和主动脉根部横切面分析来评估斑块分布。测量平均动脉压（MAP）。使用实时聚合酶链反应（PCR）分析AT1和AT2受体表达，并通过免疫组织化学确定AT2受体蛋白的定位。
仅在喂食标准饮食的小鼠中，输注Ang II可使MAP升高（P < 0.001）。无论饮食如何，输注Ang II的小鼠胸主动脉斑块面积增加22至30倍（两者均P < 0.001）。Ang II对主动脉根部斑块无影响。斑块面积不受PD123319影响。AT2受体在斑块中大量表达，高胆固醇饮食和输注Ang II可使其增加6至9倍（P < 0.01）。
Ang II增加ApoE小鼠的动脉粥样硬化程度。尽管AT2受体上调，但在该模型中我们未发现AT2受体对动脉粥样硬化形成有影响的证据。
