在骨质疏松原因中，肾素血管紧张素系统（RAS）、血管紧张素II（AngII）及产生的低Ca2+状态扮演重要角色。虽研究表明血管紧张素II受体拮抗剂（ARB）有提升机体骨量作用，但确切机理尚不清楚。AngII/ARB共同的作用靶点是血管紧张素II受体（AngIIR）。AngIIR是G蛋白偶联受体，其活化可产生多种信号分子。预实验结果证实cAMP是重要信号分子之一。据此我们推断RAS活化产生的低Ca2+状态、腺磷酸环化酶5/6活化、cAMP、PKA通路，及低Ca2+/高cAMP状态下成骨/破骨之间的失耦联（RANK-RANKL系统），在AngII/ARB-AngIIR效应机制中起到重要作用。为证实假说，本课题从器官、细胞及分子水平，首次研究AngIIR/cAMP/PKA途径及其下游事件对骨质疏松的影响，以为骨质疏松患者治疗提供一个新的药物靶点。

Among the reasons for inducing or accelarating osteoporosis, renin-angiotensin system (RAS) activation, angiotensin II (AngII) and low Ca2+ may play an essential role in the process of hypertension-related osteoporosis. Although studies have demonstrated that angiotensin II receptors blockade (ARB) is benificial for promoting bone mass, there is little underlying mechanism referred to the exact role of AngII/ARB on skeletal system. It is known that the target for both AngII and ARB is angiotensin II receptor (AngIIR). As one member of G protein-coupled receptors, AngIIR activation can produce many signalling molecules. Among these molecules, our preliminary data indicated that cAMP is an important second messenger. Therefore, we inferred that RAS activation, low Ca2+, adenylate cyclase 5/6 transactivation, cAMP, PKA, and the imbalance of osteoblastic/osteoclastic activity (RANK-RANKL system) in low Ca2+ but high cAMP microenvironment, may involve in the AngII/ARB-AngIIR effector mechanism. In order to prove hypothesis, from organ, cell and molecular levels, we firstly investigated the activation of AngIIR/cAMP/PKA pathway and the following downstream events on the process of osteoporosis, the demonstration of which may also offer a new drug targets for osteoporotic patients who at same time suffer from hypertension.