Circumventricular Organs and Cardiovascular Regulation

描述（由申请人提供）：中枢神经系统对长期血压（BP）调节的控制尚未完全了解。许多研究者研究了血管紧张素II （Angll）中枢效应中皮质下器官（SFO）和后脑区（AP）的个体作用。Angll被认为可以调节交感神经系统（SNS）和这些心室周围器官（CVOs）的活动，并调节血压（BP）。这一提议表明，Angll通过这些cvo采取的行动存在冗余。这是第一个同时检测内源性和外源性Angll对这2种CVOs影响的研究。首先，我们提出内源性Angll通过这些CVOs起作用。目标1:SFO和AP在内源性Angll的长期影响中的综合作用是什么？用AT1拮抗剂约沙坦治疗10天，测量SFOx、APx和XX大鼠的血压和心输出量（CO）。此外，我们提出内源性Angll水平的变化通过这些CVOs来调节BP。目的2：在饮食盐摄入量改变时，SFO和AP在维持血压中的联合作用是什么？对SFOx、APx和XX大鼠进行为期2周的饮食盐增加和减少，测量血压和一氧化碳。最后，我们提出慢性高血压是通过这些CVOs的作用介导的。目的3:SFO和AP在预防Angll诱导的高血压中的联合作用是什么？APx、SFOx和XX大鼠在注射Angll 10天期间测量血压和一氧化碳。我们预测XX大鼠对Iosartan的降压反应会减弱，饮食盐改变时血压失调，Angll介导的高血压也会减弱。此外，AIM3a：在Angll诱导的RVLM中，SFO和AP的联合作用是什么？在APx、SFOx和XX大鼠灌注Angll后，检测RVLM中Fos的表达。我们预测SFO和AP在Angll诱导的RVLM中表达是必需的。

DESCRIPTION (provided by applicant): Central nervous system control over long-term blood pressure (BP) regulation is not completely understood. Many investigators have studied the individual roles of the subfornical organ (SFO) and area postrema (AP) in the central effects of Angiotensin II (Angll). Angll is thought to modulate sympathetic nervous system (SNS) activityat these circumventricular organs (CVOs) and regulate blood pressure (BP). This proposal suggests there is redundancy in the actions of Angll via these CVOs. This is the first study to simultaneously examine effects of both endogenous and exogenous Angll at these 2 CVOs. First, we propose endogenous Angll acts via these CVOs. AIM 1: What are the combined roles of the SFO and AP in the long-term effects of endogenous Angll? BP and cardiac output (CO) will be measured in SFOx, APx and XX rats treated with the AT1 antagonist, Iosartan, for 10 days. Furthermore, we propose changing levels of endogenous Angll act via these CVOs to regulate BP. AIM 2: What are the combined roles of the SFO and AP in the maintenance of BP during changes in dietary salt intake? BP and CO will be measured in SFOx, APx and XX rats subjected to 2 week periods of increased and decreased dietary salt. Lastly, we propose chronic Angll hypertension is mediated through effectsat these CVOs. AIM 3: What are the combined roles of the SFO and AP in the prevention of Angll induced hypertension? BP and CO measurements will be made in APx, SFOx, and XX rats during a 10 day infusionof Angll. We predict that XX rats will have an attenuated hypotensive response to Iosartan, dysregulation of BP during changes in dietary salt, and an attenuated Angll mediated hypertension. Furthermore, AIM3a: What are the combined roles of the SFO and AP in Angll induced Fos expression in the RVLM? Fos expression will be measured in the RVLM in APx, SFOx and XX rats subjected to Angll infusion. We predicteither or both the SFO and AP are necessary for Angll induced Fos expression in the RVLM. Our hypothesis is based on the idea that lesioned animals will not be able to alter SNS activity appropriatelyin the same manner as sham rats during the above manipulations, and this will lead to the altered blood pressure responses. In order to address this underlying hypothesis, and link the SNS to the observed changes in blood pressure, we will measure acute depressor responses to the ganglionic blockingagent, hexamethonium, as well as plasma norepinephrine levels in all rats during control and treatment periods. These multiple methods will allow us to determine the sympathetic contribution to vasomotor tone during the observed changes in blood pressure. The results of these studies will greatly enhance our understanding of the central effects of Angll at two specific brain regions, and how these interactions play a role in the long-term control of arterial pressure.