Actions of Angiotensin II in Vascular Smooth Muscle

描述（由申请人提供）：血管紧张素II是一种强效血管收缩剂，其增加血管张力的作用是由AT 1受体介导的。肾外AT1A受体的缺乏使血压降低约20 mm Hg，表明肾外AT1A受体对血压慢性调节的非冗余贡献。我们假设血管平滑肌细胞中的AT1A受体的作用占肾脏外细胞系介导的血压控制的重要部分。为了测试它们影响血压调节的能力，我们将删除血管平滑肌细胞中的AT1A受体。沿着对血压的影响，我们还将确定这种基因操作对肾血流的影响。由于AT1A受体的肾血流动力学作用可影响钠排泄，从而影响血压，因此我们将进行肾交叉移植，以分离AT1A受体的全身和肾血管作用。由于AT1B受体对调节血管张力有适度的作用，我们还将在AT1B受体缺陷的背景下从血管平滑肌细胞中删除AT1A受体。

DESCRIPTION (provided by applicant): 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 approximately 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.