Levy B I, Benessiano J, Henrion D, Caputo L, Heymes C, Duriez M, Poitevin P, Samuel J L
Institut National de la Santé et de la Recherche Médicale, Unit 141, Université Denis Diderot, Paris, France.
J Clin Invest. 1996 Jul 15;98(2):418-25. doi: 10.1172/JCI118807.
Angiotensin II (Ang II) is both a vasoactive and a potent growth-promoting factor for vascular smooth muscle cells. Little is known about the in vivo contribution of AT1 and AT2 receptor activation to the biological action of Ang II. Therefore, we investigated the effect of AT1 or AT2 subtype receptor chronic blockade by losartan or PD123319 on the vascular hypertrophy in rats with Ang II-induced hypertension. Normotensive rats received for 3 wk subcutaneous infusions of Ang II (120 ng/kg per min), or Ang II + PD 123319 (30 mg/kg per d), or Ang II + losartan (10 mg/kg per d) or PD 123319 alone, and were compared with control animals. In normotensive animals, chronic blockade of AT2 receptors did not affect the plasma level of angiotensin II and the vascular reactivity to angiotensin II mediated by the AT1 receptor. Chronic blockade of AT1I in rats receiving Ang II resulted in normal arterial pressure, but it induced significant aortic hypertrophy and fibrosis. Chronic blockade of AT2 receptors in Ang II-induced hypertensive rats had no effect on arterial pressure, but antagonized the effect of Ang II on arterial hypertrophy and fibrosis, suggesting that in vivo vasotrophic effects of Ang II are at least partially mediated via AT2 subtype receptors.
血管紧张素II（Ang II）既是一种血管活性物质，也是一种对血管平滑肌细胞具有强大促生长作用的因子。关于AT1和AT2受体激活对Ang II生物学作用的体内贡献，目前了解甚少。因此，我们研究了氯沙坦或PD123319对AT1或AT2亚型受体的慢性阻断作用，对Ang II诱导的高血压大鼠血管肥厚的影响。正常血压大鼠接受为期3周的皮下输注Ang II（120 ng/kg每分钟），或Ang II + PD 123319（30 mg/kg每天），或Ang II + 氯沙坦（10 mg/kg每天），或单独使用PD 123319，并与对照动物进行比较。在正常血压动物中，慢性阻断AT2受体不影响血管紧张素II的血浆水平以及由AT1受体介导的对血管紧张素II的血管反应性。在接受Ang II的大鼠中慢性阻断AT1I导致动脉血压正常，但诱导了显著的主动脉肥厚和纤维化。在Ang II诱导的高血压大鼠中慢性阻断AT2受体对动脉血压没有影响，但拮抗了Ang II对动脉肥厚和纤维化的作用，表明Ang II在体内的血管营养作用至少部分是通过AT2亚型受体介导的。
