INTRARENAL ANGIOTENSINOGEN: LOCALIZATION & REGULATION

有相当大的兴趣在存在一个 肾内肾素血管紧张素系统（RAS）及其生理功能 影响 血管紧张素原的研究进展 大鼠和小鼠肾脏中的mRNA提供了有力的证据， 一个独立的本地RAS。 进一步支持了这一点 通过组织差异调节（例如肾脏）的演示， 与肝脏相比，血管紧张素原和肾素mRNA表达。 的 该建议的目的是采用生物化学和分子生物学技术， 肾内肾素的生物学鉴定技术 血管紧张素系统，重点是血管紧张素原（由于肾 肾素主要是分泌的，并且与血管内皮细胞的生长和/或分泌平行地变化。 循环水平）。 我们计划用原位杂交技术 技术来定位合成肾脏的细胞 血管紧张素原，并将其与肾素的定位进行比较 合成. 我们预计，这种本地化将具有强大的 血管紧张素原调节研究的意义， 功能 我们亦会研究有关表达 肾内血管紧张素原及其mRNA通过已知的 影响肾素-血管紧张素系统，重点关注 氯化钠 为了比较，我们还将研究 这些对其他成分的生理操作 肾素血管紧张素系统（AI，AII，肾素和肾素mRNA）。 选择性阻断肾素血管紧张素的成分 系统将被用来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，本申请 试图将联合收割机分子生物学技术与肾移植结合， 生理学，这可能揭示了调节 肾内肾素血管紧张素系统，也可以阐明 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.