Li J S, Touyz R M, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
Hypertension. 1998 Jan;31(1 Pt 2):487-92. doi: 10.1161/01.hyp.31.1.487.
Angiotensin II (Ang II) appears to exert its contractile and growth-promoting effects through the AT1 receptor subtype, whereas the AT2 subtype may have growth-inhibitory and proapoptotic properties. Recently, some data have challenged this emerging concept. To clarify the role of AT1 and AT2 receptors, we treated Wistar rats that were infused with Ang II (120 ng/kg/min subcutaneously by osmotic minipump), with the AT1 antagonist losartan (10 mg/kg/d in the drinking water) and the AT2 antagonist PD123319 (30 mg/kg/d subcutaneously by osmotic minipump) for 21 days. At the end of the study, tail-cuff systolic blood pressure was 106+/-2.8 mm Hg in untreated rats and 108+/-2.0 mm Hg in rats infused with Ang II that received losartan, whereas it rose to 158+/-4.9 mm Hg in Ang II-infused rats and 158+/-3.0 mm Hg in rats infused with Ang II rats and PD123319 (the two latter groups P<.01 versus the two other groups). Heart weight, and aorta cross-section/body weight ratio were higher in Ang II-infused rats than in controls and were significantly reduced in Ang II-infused rats that received losartan (P<.05). Wire-myograph-mounted coronary, renal, mesenteric, and femoral small arteries from Ang II-infused rats and Ang II-infused rats receiving PD123319 had a greater media, media cross-section, and media/lumen ratio than vessels from untreated or Ang II-infused rats treated with losartan. These results support the concept that in Wistar normotensive rats infused for 3 weeks with angiotensin II, growth in the heart, aorta, and coronary, renal, mesenteric, and femoral small arteries is mediated by the AT1 receptor; the results show little evidence of a role of AT2 receptors in mediating angiotensin II effects in this experimental paradigm.
血管紧张素II（Ang II）似乎通过AT1受体亚型发挥其收缩和促进生长的作用，而AT2亚型可能具有生长抑制和促凋亡特性。最近，一些数据对这一新兴概念提出了挑战。为了阐明AT1和AT2受体的作用，我们用AT1拮抗剂氯沙坦（饮用水中10mg/kg/d）和AT2拮抗剂PD123319（渗透微型泵皮下注射30mg/kg/d）对通过渗透微型泵皮下注射Ang II（120ng/kg/min）的Wistar大鼠进行了21天的治疗。在研究结束时，未治疗大鼠的尾袖收缩压为106±2.8mmHg，接受氯沙坦的Ang II注射大鼠为108±2.0mmHg，而在Ang II注射大鼠中升至158±4.9mmHg，在Ang II注射大鼠和PD123319注射大鼠中为158±3.0mmHg（后两组与其他两组相比P<0.01）。Ang II注射大鼠的心脏重量和主动脉横截面积/体重比高于对照组，而接受氯沙坦的Ang II注射大鼠则显著降低（P<0.05）。与未治疗或接受氯沙坦治疗的Ang II注射大鼠的血管相比，来自Ang II注射大鼠和接受PD123319的Ang II注射大鼠的安装有线肌动描记器的冠状动脉、肾动脉、肠系膜动脉和股小动脉具有更大的中膜、中膜横截面积和中膜/管腔比。这些结果支持以下概念：在Wistar正常血压大鼠中，用血管紧张素II灌注3周后，心脏、主动脉以及冠状动脉、肾动脉、肠系膜动脉和股小动脉的生长由AT1受体介导；结果几乎没有证据表明AT2受体在该实验范式中介导血管紧张素II的作用。
