INTRARENAL ANGIOTENSINOGEN: LOCALIZATION & REGULATION

有相当大的兴趣存在一种 肾内肾素血管紧张素系统(RAS)及其生理学 这意味着什么。血管紧张素原的最新文献 大鼠和小鼠肾脏中的mRNA提供了强有力的证据 存在一个独立的当地RAS。这进一步得到了支持 通过组织差异调节(例如肾脏)的演示 VS肝脏)血管紧张素原和肾素基因表达。这个 这项提议的目的是利用生化和分子 肾内肾素的生物学研究进展 血管紧张素系统，关注血管紧张素原(从肾脏开始 肾素主要是分泌的，其变化与 循环水平)。我们计划采用原位杂交技术 定位合成肾脏的细胞的技术 血管紧张素原及其与肾素定位的比较 综合。我们预计这样的本地化将会有很强的 血管紧张素原调节和血管紧张素转换酶研究的意义 功能。我们还将研究对表达的调节 肾内血管紧张素原及其信使核糖核酸 影响肾素-血管紧张素系统，侧重于 氯化钠。为了进行比较，我们还将检查这些影响 这些对其他成分水平的生理操作 肾素血管紧张素系统(AI、AII、肾素和肾素mRNA)的表达。 选择性阻断肾素-血管紧张素的成分 系统将用于研究可能的反馈调节。 在这些研究中，我们还将测量血压 以及肾功能参数。因此，此应用程序 尝试将分子生物学技术与肾脏 生理学，这可能有助于阐明 肾内肾素血管紧张素系统，也可能阐明 这个肾内系统的功能。

There has been considerable interest in the existence of an intrarenal renin angiotensin system (RAS) and its physiological implications. The recent documentation of angiotensinogen mRNA in rat and mouse kidney provides strong evidence for the presence of an independent local RAS. This is further supported by the demonstration of tissue differential regulation (e.g. kidney vs liver) of angiotensinogen and renin mRNA expression. The purposes of this proposal are to employ biochemical and molecular biology techniques to characterize the intrarenal renin angiotensin system with focus on angiotensinogen (since renal renin is primarily secreted and changes in parallel with the circulating levels). We plan to employ in situ hybridization techniques to localize the cells which synthesize renal angiotensinogen and to compare this to the localization of renin synthesis. We expect that such localization will have strong implications for studies of angiotensinogen regulation and function. We will also examine the regulation of the expression of intrarenal angiotensinogen and its mRNA by factors known to influence the renin-angiotensin system, focusing on the role of sodium chloride. For comparison we will also examine the effects these physiological manipulations on levels of other components of the renin angiotensin system (AI, AII, renin, and renin mRNA). Selective blocking of the components of the renin angiotensin system will be used to study possible feedback regulation. Throughout these studies we will also measure blood pressure as well as parameters of renal function. Thus, this application attempts to combine molecular biology techniques with renal physiology, which may shed light on the regulation of the intrarenal renin angiotensin system and may also clarify the function of this intrarenal system.