AT2 RECEPTORS IN BLOOD PRESSURE AND RENAL FUNCTION

描述(由申请人提供)：总体目标是测试 假设血管紧张素-2(AT2)受体起重要作用 在控制血压和肾功能方面通过产生 缓激肽(BK)、一氧化氮(NO)和环鸟苷3‘，5’-单磷酸 (CGMP)。其具体目的是(1)检验AT2受体的假设 刺激通过以下途径调节肾脏和全身血管扩张和低血压 增加BK、NO和cGMP的产生和(2)检验假说 AT2受体的刺激，通过增加肾脏BK、NO和 CGMP，诱导利钠。 研究人员已经证明，AT2受体表达于 肾脏、心脏和外周血管系统，刺激肾脏BK、NO和cGMP。 首席研究员对缺乏AT2受体的小鼠的最新研究 (AT2-Null)显示持续升压和抗心房利用药过敏 降至血管紧张素II(Ang II)，并伴有BK、NO、cGMP明显降低。 这些结果表明，AT2受体可能起着拮抗剂的作用 血管紧张素Ⅱ在AT1受体上的作用首席调查员最近 研究表明，注射了没有AT1受体功能的Valsartan的大鼠 AT2受体完全阻断对Ang II的降压反应 拮抗剂，PD 123319.拟议的实验代表了一种系统的方法 AT2受体在血管扩张、钠尿和肾脏中的作用 血管紧张素转换酶AT1受体阻断大鼠的上述作用机制 模特。这个模型将允许评估AT2受体和AT2受体的作用 不受功能AT1干扰的信号转导机制 感受器。 拟议的研究将阐明AT2受体在控制中的作用。 血压和肾功能。对国际货币基金组织功能的理解 AT2受体是必要的，以评估其潜在的作用，在 高血压的病理生理学，并作为抗高血压治疗的靶点。

DESCRIPTION (provided by applicant): The overall objective is to test the hypothesis that the angiotensin type-2 (AT2) receptor plays an important role in the control of blood pressure and kidney function through the generation of bradykinin (BK), nitric oxide (NO) and guanosine cyclic 3', 5' monophosphate (cGMP). The specific aims are (1) to test the hypothesis that AT2 receptor stimulation mediates renal and systemic vasodilation and hypotension by increasing the production of BK, NO and cGMP and (2) to test the hypothesis that AT2 receptor stimulation, through increased renal production of BK, NO and cGMP, induces natriuresis. The investigators have demonstrated that the AT2 receptor is expressed in the kidney, heart and peripheral vasculature and stimulates renal BK, NO and cGMP. The principal investigator's recent studies in mice lacking the AT2 receptor (AT2-Null) demonstrate a sustained pressor and antinatriuretic hypersensitivity to angiotensin II (ANG II), accompanied by a marked reduction in BK, NO, cGMP. These results suggest that the AT2 receptor may function as an opponent of the actions of ANG II at the AT1 receptor. The principal investigator has recently demonstrated that valsartan-infused rats without functioning AT1 receptors have hypotensive respoflses to Ang II that are fully blocked by the AT2 receptor antagonist, PD 123319.The proposed experiments represent a systematic approach to the role of the AT2 receptor in vasodilation and natriuresis and the renal mechanisms of these actions in the valsartan-infused (AT1 receptor-blocked) rat model. This model will allow evaluations of the role of the AT2 receptor and its signalling mechanisms in the absence of interference by functional AT1 receptors. The proposed studies will clarify the role of the AT2 receptor in the control of blood pressure and kidney function. An understanding of the function of the AT2 receptor is necessary for an assessment of its potential role in the pathophysiology of hypertension and as a target for antihypertensive therapy.