Actions of Angiotensin II in Vascular Smooth Muscle

血管紧张素 II 在血管平滑肌中的作用

• 批准号: 7156339
• 负责人: KELLY K PARSONS
• 金额: $ 4.6万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156339
• 关键词: angiotensin II; angiotensin receptor; autoradiography; blood pressure; cardiovascular pharmacology; dietary sodium; electrolyte balance; gene deletion mutation; genetically modified animals; hormone regulation /control mechanism; immunofluorescence technique; kidney circulation; kidney transplantation; laboratory mouse; muscle cells; polymerase chain reaction; postdoctoral investigator; protein localization; protein structure function; salt intake; vascular resistance; vascular smooth muscle

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.

描述（由申请人提供）：血管紧张素II是一种强大的血管收缩剂，其增加血管张力的作用是由AT1受体介导的。肾外AT1A受体的缺失使血压降低约20mm Hg，表明肾外AT1A受体对血压的慢性调节有非冗余的贡献。我们假设AT1A受体在血管平滑肌细胞中的作用在肾外细胞系介导的血压控制中起着重要作用。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。除了对血压的影响，我们还将确定这种基因操作对肾血流量的影响。由于AT1A受体的肾脏血流动力学作用会影响钠排泄从而影响血压，我们将进行肾脏交叉移植，以分离AT1A受体的全身血管和肾脏血管作用。由于AT1B受体在调节血管张力方面的作用有限，我们也将在AT1B受体缺乏的背景下从血管平滑肌细胞中删除AT1A受体。