Actions of Angiotensin II in Vascular Smooth Muscle

血管紧张素II是一种强有力的血管收缩剂，其增加血管张力的作用由AT 1介导 受体。肾外AT1A受体的缺失使血压降低约20 mm Hg， 证明了肾外AT1A受体对血液慢性调节的非冗余贡献 压力我们假设血管平滑肌细胞中的AT1A受体的作用解释了 血压控制的很大一部分是由肾脏外的细胞系介导的。测试他们 影响血压调节的能力，我们将删除AT1A受体，特别是在血管平滑 肌肉细胞沿着对血压的影响，我们还将确定这种遗传的后果。 对肾血流的影响。因为AT1A受体的肾血流动力学作用可能影响 钠排泄，从而影响血压，我们将进行肾脏交叉移植， 分离AT1A受体的全身和肾血管作用。由于AT1B受体具有适度的 为了调节血管张力，我们还将从血管平滑肌细胞中删除AT1A受体， AT1B受体缺乏背景。

Angiotensin II is a powerful vasoconstrictor and its actions to increase vascular tone are mediated by AT1 receptors. The absence of extra-renal AT1A receptors reduces blood pressure by ~20mm Hg, demonstrating a non-redundant contribution of extra-renal AT1A receptors to chronic regulation of blood pressure. We hypothesize that the effects of AT1A receptors in vascular smooth muscle cells account for a significant portion of blood pressure control mediated by cell lineages outside the kidney. To test their capacity to affect blood pressure regulation, we will delete AT1A receptors specifically in vascular smooth muscle cells. Along with effects on blood pressure, we will also determine the consequences of this genetic manipulation on renal blood flow. Because renal hemodynamic actions of AT1A receptors could impact sodium excretion and thereby affect blood pressure, we will carry out kidney cross-transplants in order to separate the systemic and renal vascular actions of AT1A receptors. As AT1B receptors have modest effects to regulate vascular tone, we will also delete AT1A receptors from vascular smooth muscle cells on an AT1B receptor-deficient background.